Affinage

QKI

KH domain-containing RNA-binding protein QKI · UniProt Q96PU8

Length
341 aa
Mass
37.7 kDa
Annotated
2026-06-10
100 papers in source corpus 43 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

QKI is a STAR-family RNA-binding protein that governs post-transcriptional gene expression across myelination, cell differentiation, metabolism, and tumor biology, expressed as three isoforms with distinct subcellular distributions—nuclear QKI-5, perikaryal QKI-6, and cytoplasmic QKI-7 (PMID:8987822). QKI proteins self-associate through the QUA1 domain, and QKI-5 carries a dedicated STAR-NLS that drives nucleocytoplasmic shuttling (PMID:10506177), while sequence-specific recognition depends on bipartite UAAY-type QKI response elements (QREs) (PMID:19457263). Through these elements QKI controls target mRNA fate in opposing directions: it stabilizes transcripts such as MBP and MAP1B (PMID:10864952, PMID:16855020) and destabilizes others including AIP-1, FOXO1, and RASA1 (PMID:20631256, PMID:24398626, PMID:27767378), with MBP-binding activity switched off by Src-PTK tyrosine phosphorylation during myelin development (PMID:12682013). The isoforms partition mechanistically—nuclear QKI-5/QKI-6 regulate alternative splicing of hundreds of targets (NUMB, ADD3, macroH2A1, Itga7, and sarcomeric genes) in part by competing with the splicing factor SF1 at branchpoints (PMID:24722255, PMID:33196842), and retain pri-miRNAs in nuclear foci with Drosha to block miRNA maturation (PMID:23319046), whereas cytoplasmic QKI-7 recruits the non-canonical poly(A) polymerase PAPD4/GLD-2 to promote cytoplasmic polyadenylation and adenylation of target mRNAs and miR-122 (PMID:26926106, PMID:31792053). QKI further reads internal m7G-modified mRNAs and shuttles them into stress granules via G3BP1 to tune their translation (PMID:37379838), and modulates AGO2/miRNA-mediated silencing as an auxiliary factor (PMID:38372062). Beyond RNA, QKI acts on chromatin as a transcriptional co-activator, binding single-stranded promoter DNA to recruit Srebp2 and the PPARβ-RXRα complex to drive cholesterol and lipid biosynthesis required for myelin (PMID:32202512, PMID:34021134, PMID:33942715). These activities converge on biological programs spanning oligodendrocyte and Schwann cell myelination (PMID:8987822, PMID:17079655, PMID:19517016), microglial myelin-debris clearance (PMID:33045062), cardiac sarcomerogenesis (PMID:33397958, PMID:36627242), muscle stem cell asymmetric division (PMID:35165120), adipose thermogenesis (PMID:31868295), and post-transcriptional control of Notch, Ras-MAPK, NF-κB, and Wnt pathway components (PMID:24722255, PMID:27767378, PMID:32382069, PMID:37460362).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Established that QKI is expressed as isoforms with divergent subcellular localizations linked to myelinating cells, framing isoform identity as the basis of functional specialization.

    Evidence Isoform-specific antibody immunostaining in mouse nervous tissue and quaking-viable mutants

    PMID:8987822

    Open questions at the time
    • Did not define the molecular activity of each isoform
    • Did not identify RNA targets
  2. 1999 High

    Defined the structural logic of QKI function by mapping self-dimerization to the QUA1 domain and identifying a STAR-NLS that confers QKI-5 nucleocytoplasmic shuttling, explaining the isoforms' differential localization.

    Evidence GFP fusion localization, QUA1 mutagenesis, interspecies heterokaryon shuttling assay

    PMID:10506177

    Open questions at the time
    • Did not establish RNA-binding consequences of dimerization
    • Shuttling cargo not identified
  3. 1999 High

    Demonstrated that QKI is a sequence-specific translational repressor acting through 3' UTR elements, providing the first direct functional mechanism.

    Evidence In vitro binding, in vivo C. elegans reporter, genetic epistasis with tra-3

    PMID:10535969

    Open questions at the time
    • Endogenous mammalian targets not yet defined
    • Repression mechanism at molecular level unresolved
  4. 2000 High

    Identified MBP mRNA as a physiological QKI target and showed QKI stabilizes and localizes it, connecting QKI molecular activity to the myelination phenotype.

    Evidence RNase protection, RNA fractionation, RNA-protein interaction, 3' UTR deletion in qkv mice

    PMID:10864952

    Open questions at the time
    • Mechanism of mRNA stabilization vs localization not separated
    • Regulation of QKI binding not addressed
  5. 2003 High

    Revealed that QKI RNA binding is dynamically controlled by Src-PTK tyrosine phosphorylation, providing a developmental switch for myelin gene expression.

    Evidence RNA-protein interaction and phosphorylation assays with in vivo developmental time-course

    PMID:12682013

    Open questions at the time
    • Specific phosphosites and kinases not fully resolved
    • Generalizability to non-MBP targets unknown
  6. 2006 High

    Expanded the target repertoire (MAP1B) and established isoform-specific requirements for oligodendrocyte differentiation, showing RNA-binding is essential for QKI's pro-differentiation function.

    Evidence RIP, RNAi, forced expression, point mutation of RNA-binding domain, transgenic rescue, EM in qkv mice

    PMID:16855020 PMID:17079655 PMID:17575274

    Open questions at the time
    • Full target set in differentiation undefined
    • Distinct contributions of stabilization vs splicing not separated
  7. 2009 High

    Defined the QKI binding motif as bipartite UAAY repeats and extended QKI's myelination role to Schwann cells, generalizing the recognition code across STAR proteins.

    Evidence SELEX and in vitro binding; PNS co-culture gain/loss-of-function with EM

    PMID:19457263 PMID:19517016

    Open questions at the time
    • In vivo motif occupancy not mapped
    • Structural basis of bipartite recognition not resolved
  8. 2010 High

    Showed QKI can destabilize target mRNAs (AIP-1) and physically associates with Ago2 in stress granules, broadening its repertoire to mRNA decay and RNAi machinery.

    Evidence 2D-DIGE proteomics, mRNA stability assay, qkv mice; Co-IP and co-localization with Ago2

    PMID:20631256 PMID:20862255

    Open questions at the time
    • Ago2 interaction from single Co-IP without reciprocal validation
    • Determinants of stabilize-vs-destabilize choice unknown
  9. 2011 High

    Established QKI as an alternative-splicing regulator and embedded it in a cell-cycle transcriptional circuit (E2F1 feedback) and a QKI→PLP→SIRT2 myelin pathway, broadening function beyond mRNA stability.

    Evidence Splicing microarray/RT-PCR (macroH2A1), ChIP and luciferase (E2F1), genetic rescue (PLP/SIRT2)

    PMID:21768773 PMID:21844227 PMID:21948283

    Open questions at the time
    • Splicing mechanism not yet mechanistic
    • Direct vs indirect transcriptional effects not fully separated
  10. 2013 High

    Uncovered a nuclear-isoform-specific mechanism—retention of pri-miRNA with Drosha to block miRNA biogenesis—and direct 3' UTR repression of FOXO1, linking QKI to EGFR/ERK signaling and cancer.

    Evidence Nuclear fractionation, RIP, Drosha co-IP, miR-7 rescue; RIP and mRNA stability for FOXO1

    PMID:23319046 PMID:24398626

    Open questions at the time
    • Generality of pri-miRNA retention beyond miR-7-1 untested
    • FOXO1 finding single-lab
  11. 2014 High

    Resolved a splicing mechanism in which QKI-5 competes with SF1 at the branchpoint to control NUMB and gate Notch signaling, and extended 3' UTR control to SOX2 and cardiac FoxO1.

    Evidence Splicing reporter and SF1 competition binding (NUMB); RIP/QRE mapping (SOX2); in vivo I/R model (FoxO1)

    PMID:24722255 PMID:24918581 PMID:25068621

    Open questions at the time
    • Generality of SF1 competition across targets not established
    • SOX2 and FoxO1 findings single-lab
  12. 2016 High

    Defined QKI-7 as the cytoplasmic-polyadenylation isoform via PAPD4/GLD-2 recruitment and mapped transcriptome-wide binding by iCLIP, linking binding position to splicing direction and to Ras-MAPK control via RASA1.

    Evidence Co-IP, poly(A) and tethered reporter assays (QKI-7/PAPD4); iCLIP-seq (ADD3); RIP/stability (RASA1)

    PMID:26926106 PMID:27767378 PMID:33196842

    Open questions at the time
    • Rules governing position-dependent splicing incompletely defined
    • RASA1 finding single-lab
  13. 2019 High

    Established QKI as a chromatin-acting transcriptional co-activator of PPARβ-RXRα and broadened isoform-specific roles to vascular, endothelial, adipose, and lipid-uptake programs.

    Evidence Oligodendrocyte conditional KO with lipidomics and agonist rescue (PPARβ); RIP/splicing (HDAC7), mRNA decay (CD144/NLGN1/TSG-6), conditional KO (UCP1/PGC1α); luciferase (SRA); GLD-2/Ago2 adenylation of miR-122

    PMID:26056009 PMID:28186995 PMID:31331967 PMID:31792053 PMID:31868295 PMID:32202512 PMID:32732889

    Open questions at the time
    • Mechanism of QKI recruitment to nuclear receptor complexes incompletely defined
    • Several tissue findings single-lab
  14. 2021 High

    Cemented QKI's dual nucleic-acid roles—single-stranded DNA-binding co-activation of Srebp2 cholesterol biosynthesis and broad splicing/RNA-stability control of cardiac, microglial, muscle, immune, and Wnt programs.

    Evidence ChIP and Co-IP (Srebp2/Pol II) with conditional KO and sterol rescue; conditional KOs and CRISPR in microglia, cardiomyocytes, muscle stem cells, macrophages, and BMSCs with transcriptomic/functional readouts

    PMID:32382069 PMID:33045062 PMID:33397958 PMID:33758177 PMID:33942715 PMID:34021134 PMID:37460362

    Open questions at the time
    • How QKI selects DNA vs RNA targets unresolved
    • Several lineage phenotypes from single labs
  15. 2023 High

    Identified QKI as a reader of internal m7G-modified mRNAs that, via G3BP1, routes transcripts into stress granules and reshapes translation, and defined an auxiliary role in AGO2/let-7b silencing.

    Evidence Transcriptome-wide m7G profiling, G3BP1 Co-IP, stress granule imaging, translation assay; PAR-CLIP, AGO-depleted cells, single-molecule imaging

    PMID:37379838 PMID:38372062

    Open questions at the time
    • Structural basis of m7G recognition not resolved
    • Interplay between m7G reading and QRE binding unclear
  16. 2024 High

    Showed QKI controls alternative polyadenylation site choice to regulate lncRNA isoform balance (NEAT1) and paraspeckle-driven glioma migration, adding 3'-end processing to its mechanistic repertoire.

    Evidence CRISPR-Cas9 PAS deletion, RNA-binding and isoform quantification, migration assay

    PMID:39032650

    Open questions at the time
    • Generality of QKI-directed APA across transcriptome untested
    • Mechanism linking QKI binding to PAS selection unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How QKI integrates its many partial mechanisms—choosing among stabilization, destabilization, splicing, polyadenylation, m7G reading, and DNA-binding co-activation at a given target—remains unresolved.
  • No unifying model for target-by-target outcome selection
  • No structural determinant distinguishing DNA vs RNA engagement
  • Crosstalk between phosphorylation, isoform identity, and partner availability not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 11 GO:0045182 translation regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2 GO:0005730 nucleolus 1
Pathway
R-HSA-8953854 Metabolism of RNA 8 R-HSA-1266738 Developmental Biology 5 R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 3
Partners
AGO2DROSHAG3BP1PAPD4PPARDSF1SREBF2
Complex memberships
stress granule

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 QKI isoforms show distinct subcellular localizations: QKI-5 is restricted to the nucleus, whereas QKI-6 and QKI-7 are localized to the perikaryal cytoplasm. In quakingviable mutants, QKI-6 and QKI-7 are absent exclusively from myelin-forming cells, while QKI-5 is absent only in oligodendrocytes of severely affected tracts, implicating these isoforms as regulators of myelination. Immunostaining with antibodies raised to unique carboxy peptides of QKI isoforms in mouse nervous system tissue The Journal of Neuroscience High 8987822
1999 QKI isoforms can associate with each other (dimerize), and the QUA1 domain is responsible for QKI self-interaction; a single amino acid change in QUA1 (qkI kt4 lethal mutation) abolishes self-interaction. QKI-5 contains a novel 7-amino acid nuclear localization sequence (STAR-NLS) in its unique C-terminus, and QKI-5 (but not ETLE) shuttles between the nucleus and cytoplasm as shown by interspecies heterokaryon assay. GFP fusion protein localization, interspecies heterokaryon shuttling assay, mutagenesis of QUA1 domain The Journal of Biological Chemistry High 10506177
1999 QKI-6 functions as a translational repressor by specifically binding to TGE (tra-2 and GLI elements) sequences in 3' UTRs, repressing translation of reporter constructs containing TGEs both in vitro and in vivo. Expression of QKI-6 in C. elegans causes somatic masculinization consistent with repression of tra-2. In vitro binding assay, in vivo reporter assay in C. elegans, genetic epistasis with tra-3 loss-of-function Proceedings of the National Academy of Sciences High 10535969
2000 QKI binds to the 3' UTR of myelin basic protein (MBP) mRNAs and this interaction stabilizes MBP mRNAs. In qkv/qkv mice lacking QKI, isoform-preferential destabilization of MBP mRNAs occurs in the cytoplasm, and MBP mRNAs fail to localize to the myelin membrane fraction, instead accumulating in membrane-free polyribosomes. RNase protection assay, RNA fractionation, RNA-protein interaction assay, 3'UTR deletion analysis The Journal of Neuroscience High 10864952
2003 Tyrosine phosphorylation of QKI by Src family protein tyrosine kinases (Src-PTKs) negatively regulates QKI's interaction with MBP mRNA. During early myelin development, tyrosine phosphorylation of QKI declines, leading to enhanced QKI-MBP mRNA interactions, MBP mRNA accumulation, and accelerated myelinogenesis. RNA-protein interaction assay, phosphorylation assay, developmental time-course in vivo The EMBO Journal High 12682013
2006 QKI binds to the 3' UTR of MAP1B mRNA via QKI response elements, and QKI-deficiency in quakingviable oligodendrocytes results in reduced MAP1B mRNA. RNAi-mediated QKI knockdown destabilizes MAP1B mRNA in CG4 cells, and forced QKI expression promotes MAP1B expression, demonstrating QKI-dependent post-transcriptional stabilization of MAP1B mRNA specifically in oligodendroglia. RNA immunoprecipitation, RNAi knockdown, forced expression, qkv mutant mice analysis Molecular Biology of the Cell High 16855020
2006 QKI-6 is the predominant isoform responsible for CNS myelination. Transgenic QKI-6 expression specifically in oligodendroglia rescues the severe tremor and hypomyelination of qkV/qkV mutant mice, restores compact myelin with normal lamellar periodicity, and preferentially associates with MBP mRNA to rescue MBP expression. QKI-6 binds PLP mRNA with lower efficiency. Transgenic rescue experiment, electron microscopy, RNA immunoprecipitation, qkV mutant mice The Journal of Neuroscience High 17079655
2007 Each QKI isoform (QKI-5, QKI-6, QKI-7) is sufficient to enhance oligodendrocyte progenitor cell (OPC) differentiation with different efficiencies; a point mutation abrogating RNA binding activity abolishes this function. QKI knockdown blocks OPC differentiation and can be partially rescued by QKI-5 and QKI-6 but not QKI-7, indicating differential isoform requirements independent of cell cycle exit. siRNA knockdown, forced expression, point mutation analysis of RNA-binding domain, OPC differentiation assay The Journal of Biological Chemistry High 17575274
2009 STAR proteins QKI, GLD-1, SAM68, and SLM-2 all recognize bipartite RNA motifs (direct repeats). QKI requires both halves of a bipartite UAAY consensus (SELEX-defined) for high-affinity binding. GLD-1 also binds bipartite RNA sequences from its physiological tra-2 target. SELEX (Systematic Evolution of Ligands by Exponential enrichment), in vitro binding assays BMC Molecular Biology High 19457263
2009 QKI-6 and QKI-7 block Schwann cell proliferation and promote Schwann cell differentiation and myelination in PNS co-cultures. Expression of QKI-6 and QKI-7 elevated p27KIP1 and MBP protein levels as markers of Schwann cell differentiation, and QKI-deficient Schwann cells showed reduced MBP, p27KIP1, and Krox-20 mRNAs. Ectopic expression in dorsal root ganglia co-cultures, electron microscopy, RT-PCR, siRNA knockdown PLoS One High 19517016
2010 QKI-6 decreases the half-life of actin-interacting protein 1 (AIP-1) mRNA by binding to a QKI response element in the AIP-1 3' UTR. During oligodendrocyte differentiation, increased QKI-6 parallels decreased AIP-1 expression; qkv/qkv mice lacking QKI-6/7 show increased AIP-1 in OLs. AIP-1 knockdown causes defects in OL process outgrowth. 2D-DIGE proteomics to identify target, RNA stability assay, QKI response element mapping, qkv mutant mice, siRNA knockdown Molecular Biology of the Cell High 20631256
2010 QKI-6 interacts with Argonaute 2 (Ago2) and co-localizes with Ago2 and MBP mRNA in cytoplasmic stress granules of glial cells. Co-immunoprecipitation, co-localization imaging in glial cells PLoS One Medium 20862255
2011 SIRT2 abundance in CNS myelin is regulated by a QKI-PLP pathway: in qkv/qkv OL-specific QKI-deficient mice, PLP (but not DM20) mRNA is selectively down-regulated and SIRT2 protein is severely reduced while SIRT2 mRNA remains unaffected. Rescue of SIRT2 expression requires restoration of PLP by QKI-6 expression in oligodendrocytes. qkv mutant mice analysis, transgenic QKI-6 rescue, QRT-PCR, Western blot Glia High 21948283
2011 QKI regulates alternative splicing of macroH2A1 pre-mRNA, promoting inclusion of the macroH2A1.1 isoform. RNAi-mediated QKI knockdown increases macroH2A1.1 levels, and QKI expression is significantly reduced in many cancers that show reduced macroH2A1.1 splicing. RNAi, splicing microarray, RT-PCR validation Molecular and Cellular Biology Medium 21844227
2011 E2F1 directly transcribes QKI by binding to a -542~-538 E2F1 binding site in the QKI promoter (confirmed by ChIP). Increased QKI in turn reduces E2F1 activity and delays S-phase entry, forming a negative feedback loop. QKI overexpression increased p27 and decreased cyclin D1 and c-fos; p27 and c-fos are direct QKI mRNA targets. Promoter luciferase assay, ChIP, forced expression, cell cycle analysis Cell Cycle High 21768773
2013 QKI-5 and QKI-6, but not QKI-7, inhibit the processing of primary miR-7-1 to mature miR-7 in a QKI response element (QRE)-specific manner. The nuclear QKI isoforms tightly retain pri-miR-7-1 RNA in nuclear foci and keep it associated with Drosha, preventing its processing. QKI-deficient cells show elevated miR-7, reduced EGFR expression, decreased ERK activation, and defects in cell proliferation. siRNA knockdown, nuclear fractionation, RNA immunoprecipitation, cell proliferation assay, miR-7 inhibitor rescue Molecular and Cellular Biology High 23319046
2014 QKI-5 regulates alternative splicing of NUMB pre-mRNA by binding to two QRE elements, suppressing a pro-proliferative NUMB isoform and thereby preventing activation of the Notch signaling pathway. QKI-5 inhibits splicing by competing with the core splicing factor SF1 for binding to the branchpoint sequence. RNA binding assay, splicing reporter assay, competing binding with SF1, cell proliferation assay, in vitro and in vivo experiments PLoS Genetics High 24722255
2013 QKI directly binds the 3' UTR of FOXO1 mRNA and decreases its mRNA stability, resulting in post-transcriptional repression of FOXO1 expression in breast cancer cells. QKI knockdown restores FOXO1 expression; ATRA-induced increase in FOXO1 is dependent on QKI-mediated post-transcriptional regulation. RNA immunoprecipitation, mRNA stability assay, siRNA knockdown, forced expression Oncology Reports Medium 24398626
2016 QKI-5 regulates alternative splicing of ADD3 (Adducin 3) exon 14 by binding to multiple sites in an upstream intron region as mapped by iCLIP-seq. QKI-5 binding position determines whether it promotes or represses splicing of target exons. QKI tumor-associated mutations dysregulate splicing of ADD3 and NUMB targets. iCLIP-seq (nucleotide-resolution in vivo binding), RT-PCR splicing assays, mutagenesis of QKI binding sites, overexpression/knockdown Journal of Molecular Cell Biology High 33196842
2016 QKI-5 stabilizes RASA1 mRNA via direct binding to the QKI response element region of RASA1, preventing activation of the Ras-MAPK signaling pathway and suppressing ccRCC cell proliferation. RNA immunoprecipitation, mRNA stability assay, RASA1 knockdown, cell proliferation assay Cell Cycle Medium 27767378
2016 The STAR protein QKI-7 (cytoplasmic isoform) recruits the non-canonical poly(A) polymerase PAPD4 through its unique carboxyl-terminal region to promote cytoplasmic polyadenylation and translation of target mRNAs (hnRNPA1, p27kip1, and β-catenin) in a QKI response element-dependent manner. Only QKI-7, not nuclear isoforms, promotes poly(A) tail extension. An anti-mitogenic signal induces cell cycle arrest at G1 through QKI-7/PAPD4-mediated polyadenylation of p27kip1 mRNA. Transcriptional pulse-chase analysis, tethered reporter assay, co-immunoprecipitation of QKI-7 and PAPD4, poly(A) length assay, translation assay Nucleic Acids Research High 26926106
2019 QKI-7 uses its C-terminal region to interact with the poly(A) polymerase GLD-2 (PAPD4) and its QUA2 domain to associate with Argonaute 2 (Ago2), thereby recruiting GLD-2 to Ago2. QKI-7 shows specific affinity for miR-122 and significantly promotes GLD-2-mediated 3' adenylation of miR-122 in vitro, stabilizing mature miR-122. Co-immunoprecipitation, in vitro adenylation assay, QKI isoform-specific knockdown, RNA binding assay The Journal of Biological Chemistry High 31792053
2019 QKI-6 binds to the HDAC7 intron 1 via the QKI-binding motif upon PDGF-BB stimulation to promote HDAC7 alternative splicing, driving VSMC differentiation from iPSCs. QKI-6 transcriptionally activates SM22 (TAGLN) and QKI-6 knockdown diminishes differentiation capability. RNA immunoprecipitation, splicing assay, overexpression/knockdown, iPSC differentiation assay, in vivo angiogenesis Journal of Cell Science Medium 31331967
2019 QKI-7 expression in endothelial cells is controlled by RNA splicing factors CUG-BP and hnRNPM through direct binding. QKI-7 upregulation promotes mRNA degradation of downstream targets CD144, Neuroligin 1 (NLGN1), and TNF-α-stimulated gene 6 (TSG-6) as shown by RNA immunoprecipitation and mRNA-decay assays, causing endothelial cell dysfunction in diabetes. RNA immunoprecipitation (RIP), mRNA-decay assay, QKI-7 knockdown in vivo (hindlimb ischemia mouse model) Nature Communications High 32732889
2019 QKI restricts adipose tissue energy consumption by decreasing stability, nuclear export, and translation of UCP1 and PGC1α mRNAs. QKI is transcriptionally induced by the cAMP-CREB axis in adipose tissue, and QKI-deficient mice are resistant to high-fat-diet-induced obesity with enhanced thermogenesis. Adipose tissue-specific QKI knockout mice, mRNA stability assay, nuclear export assay, translation assay, metabolic phenotyping EMBO Reports High 31868295
2019 QKI-5 directly binds the 3' UTR of SOX2 mRNA via QRE elements, reducing SOX2 expression and thereby impairing oral cancer stem cell sphere formation and self-renewal. RNA immunoprecipitation, QRE deletion/mutation assay, sphere formation assay, in vivo tumor implantation Cancer Biology & Therapy Medium 24918581
2020 Qki serves as a transcriptional co-activator of the PPARβ-RXRα nuclear receptor complex, controlling transcription of lipid metabolism genes (fatty acid desaturation and elongation). Oligodendrocyte-specific Qki depletion causes rapid demyelination through loss of myelin lipids (monounsaturated and very-long-chain fatty acids) without affecting major myelin proteins; this is rescued by high-fat diet or PPARβ/RXR agonists. Oligodendrocyte-specific conditional Qki knockout, lipidomic analysis, PPARβ/RXR agonist treatment, in vivo rescue experiment The Journal of Clinical Investigation High 32202512
2021 Qki-5 functions as a co-activator of Srebp2 to control transcription of cholesterol biosynthesis genes in oligodendrocytes, demonstrated by Qki directly interacting with single-stranded DNA and recruiting Srebp2 and RNA Pol II to promoter regions. Qki depletion reduces cholesterol in mouse brain and causes cataract in lens cells; these defects are rescued by topical sterol administration. ChIP, co-IP of Qki with Srebp2/Pol II, lens-specific and neural stem cell-specific conditional knockout, lipidomic analysis, sterol rescue Nature Communications / eLife High 33942715 34021134
2021 Qki in microglia is required for the clearance of myelin debris; microglial Qki deletion impairs phagosome formation and maturation gene splicing and RNA stability. RNA immunoprecipitation confirmed physical interactions between Qki protein and mRNAs of phagocytosis genes including Cd36. Qki depletion in microglia impaired axon integrity, oligodendrocyte maturation, and remyelination. Microglial conditional Qki knockout, RNA immunoprecipitation, transcriptomic analysis, phagocytosis assay, demyelination model The Journal of Experimental Medicine High 33045062
2021 QKI is indispensable for cardiac sarcomerogenesis through regulation of alternative splicing of genes involved in Z-disc formation and contractile physiology. QKI-deficient hESC-derived cardiomyocytes fail to transition into functional cardiomyocytes; Qki-deficient mouse hearts recapitulate these splicing and structural defects. CRISPR/Cas9 QKI deletion in hESCs, RNA-seq transcriptomic analysis, Qki-deficient mouse model, sarcomere structural analysis Nature Communications High 33397958
2021 QKI deficiency in macrophages promotes RANKL-induced osteoclastogenesis by amplifying NF-κB and MAPK signaling cascades, upregulating NFATc1 activity, and increasing osteoclast-specific markers. Additionally, QKI deficiency inhibits osteoblast formation through inflammatory microenvironment effects. Monocyte/macrophage-specific QKI knockout mouse, osteoclast differentiation assay, Western blot for NF-κB/MAPK pathways, TRAP staining Cell Death & Disease Medium 32382069
2021 QKI depletion in macrophages facilitates nuclear export of Keap1 mRNA to the cytoplasm following LPS stimulation, increasing cytoplasmic Keap1 expression and consequently weakening NRF2 nuclear activation and antioxidant capacity. QKI-deficient macrophage mice show amplified oxidative stress and aggravated IBD. Macrophage-specific QKI knockout mice, shRNA knockdown, nuclear/cytoplasmic fractionation of Keap1 mRNA, DSS-induced colitis model Cell Death Discovery Medium 33758177
2021 QKI is a critical regulator of alternative splicing of Integrin Alpha-7 (Itga7) in muscle stem cells. Conditional QKI knockout in MuSCs results in reduced asymmetric cell divisions, loss of myogenic progenitor population, and muscle regeneration defects. Antisense oligonucleotide recapitulating the single QKI-dependent Itga7 splicing event (X1 to X2 shift) impairs Itga7 and Dmd polarization. Conditional QKI knockout mouse, transcriptomic analysis, antisense oligonucleotide splicing manipulation, asymmetric division assay Life Science Alliance High 35165120
2023 QKI-7 interacts with stress granule core protein G3BP1 via its C-terminus and shuttles internally m7G-modified mRNAs into stress granules to regulate their stability and translation. QKI proteins selectively recognize internal m7G modifications in mRNAs with a conserved GANGAN motif. QKI7 attenuates translation of Hippo signaling pathway genes, sensitizing cancer cells to chemotherapy. Transcriptome-wide m7G profiling, QKI binding site mapping, Co-IP of QKI-7 and G3BP1, stress granule imaging, translation assay Cell High 37379838
2023 QKI regulates the alternative splicing of more than 1000 genes in adult cardiomyocytes, including sarcomere, cytoskeletal, calcium-handling, and transcriptional regulators, producing muscle-specific isoforms. Cardiomyocyte-specific QKI deletion causes embryonic lethality and tamoxifen-inducible adult deletion causes rapid heart failure with sarcomere disruption within 7 days. QKI overexpression in neonatal rat ventricular myocytes directs splicing in the opposite direction and enhances contractility. Conditional cardiomyocyte-specific Cre-Lox knockout, tamoxifen-inducible knockout, RNA-seq, forced overexpression in neonatal cardiomyocytes, contractility measurement Cardiovascular Research High 36627242
2024 QKI promotes the utilization of the NEAT1 proximal polyadenylation site (PAS) by binding to proximal QKI recognition elements, thereby controlling NEAT1 isoform balance (NEAT1_1 vs NEAT1_2) in glioma cells. CRISPR-Cas9-mediated PAS deletion reduces NEAT1_1 and increases NEAT1_2, enhancing nuclear paraspeckle formation and driving glioma cell migration. CRISPR-Cas9 PAS deletion, isoform-specific quantification assay, RNA-protein binding assay, transcriptomic analysis, cell migration assay The Journal of Biological Chemistry High 39032650
2024 QKI acts as an auxiliary factor in AGO2/let-7b-mediated gene silencing: QKI depletion decreases AGO2 interaction with let-7b and target mRNA, accelerating target mRNA decay loss. QKI suppresses dissociation of let-7b from AGO2 and slows assembly of AGO2/miRNA/target mRNA complexes at the single-molecule level. QKI overexpression suppresses cMYC expression post-transcriptionally and decreases proliferation and migration. PAR-CLIP, AGO-depleted cell lines, single-molecule imaging, Co-IP of QKI-AGO2, mRNA decay assay, functional proliferation/migration assay RNA Biology High 38372062
2019 QKI suppresses scavenger receptor A (SRA) at the transcriptional level by binding to QRE elements in SRA mRNA 3'UTR, reducing lipid uptake in macrophages. miR-29a during monocyte-to-macrophage differentiation directly targets QKI, suppressing QKI and allowing SRA upregulation. Luciferase reporter assay for 3'UTR binding, QKI overexpression/knockdown, lipid uptake functional assay, miR-29a mimics and inhibitors Biochemical and Biophysical Research Communications Medium 26056009
2014 QKI-5 deficiency in diabetic ob/ob myocardium contributes to FoxO1 overactivation; forced QKI-5 expression destabilizes FoxO1 mRNA in cardiomyocytes, reducing FoxO1 protein and subsequent nitrosative and ER stress, thereby reducing ischemia/reperfusion injury. siRNA and adenovirus-mediated QKI-5 manipulation in vivo (intramyocardial injection), mRNA stability assay, in vivo myocardial I/R model Journal of Molecular and Cellular Cardiology Medium 25068621
2017 QKI regulates transcription of smooth muscle cell genes (SRF, MEF2C, Myocd) through direct binding to their promoters during embryonic stem cell-to-VSMC differentiation. miR-214 targets QKI 3'UTR to suppress QKI expression, thereby de-repressing VSMC gene expression during differentiation. Luciferase assay for QKI 3'UTR targeting, chromatin binding to promoters, overexpression/knockdown in differentiating ESCs, in vivo differentiation Oncotarget Medium 28186995
2020 TR4 transcriptionally increases QKI expression to increase circZEB1 levels, which sponges miR-141-3p to increase ZEB1 expression, altering prostate cancer radiosensitivity. Chromatin immunoprecipitation (ChIP) for TR4 binding to QKI promoter, circRNA quantification, miRNA sponge assay, in vivo PCa mouse model Cancer Letters Medium 32768524
2021 QKI-5 represses the expressions of Wnt pathway genes Wnt5b, Fzd7, Dvl3, and β-catenin via direct binding to their mRNA specific sites in bone marrow stromal cells, suppressing osteogenic differentiation and activating canonical Wnt pathway. RIP-seq, RNA FISH, RIP-qPCR, BMSC-specific QKI transgenic and knockout mice, osteogenic differentiation assay Archives of Medical Research Medium 37460362

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. Nature genetics 216 26829751
2014 The RNA-binding protein QKI suppresses cancer-associated aberrant splicing. PLoS genetics 198 24722255
2006 Human QKI, a potential regulator of mRNA expression of human oligodendrocyte-related genes involved in schizophrenia. Proceedings of the National Academy of Sciences of the United States of America 171 16641098
1996 Neural cell type-specific expression of QKI proteins is altered in quakingviable mutant mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 149 8987822
2023 QKI shuttles internal m7G-modified transcripts into stress granules and modulates mRNA metabolism. Cell 139 37379838
2011 QKI-mediated alternative splicing of the histone variant MacroH2A1 regulates cancer cell proliferation. Molecular and cellular biology 132 21844227
2018 LncRNA MEG3 inhibits the progression of prostate cancer by modulating miR-9-5p/QKI-5 axis. Journal of cellular and molecular medicine 125 30565858
2000 Destabilization and mislocalization of myelin basic protein mRNAs in quaking dysmyelination lacking the QKI RNA-binding proteins. The Journal of neuroscience : the official journal of the Society for Neuroscience 124 10864952
2016 MiR-143-3p functions as a tumor suppressor by regulating cell proliferation, invasion and epithelial-mesenchymal transition by targeting QKI-5 in esophageal squamous cell carcinoma. Molecular cancer 122 27358073
1999 The quaking I-5 protein (QKI-5) has a novel nuclear localization signal and shuttles between the nucleus and the cytoplasm. The Journal of biological chemistry 120 10506177
1999 Genomic organization and expression analysis of the mouse qkI locus. Mammalian genome : official journal of the International Mammalian Genome Society 100 10384037
1999 The STAR protein QKI-6 is a translational repressor. Proceedings of the National Academy of Sciences of the United States of America 97 10535969
2006 Human QKI, a new candidate gene for schizophrenia involved in myelination. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 90 16342280
2021 QKI is a critical pre-mRNA alternative splicing regulator of cardiac myofibrillogenesis and contractile function. Nature communications 87 33397958
2006 The human homolog of the QKI gene affected in the severe dysmyelination "quaking" mouse phenotype: downregulated in multiple brain regions in schizophrenia. The American journal of psychiatry 76 17012699
2013 The QKI-5 and QKI-6 RNA binding proteins regulate the expression of microRNA 7 in glial cells. Molecular and cellular biology 73 23319046
2003 Defective smooth muscle development in qkI-deficient mice. Development, growth & differentiation 69 14706070
2016 A large-scale analysis of alternative splicing reveals a key role of QKI in lung cancer. Molecular oncology 67 27555542
2009 The STAR RNA binding proteins GLD-1, QKI, SAM68 and SLM-2 bind bipartite RNA motifs. BMC molecular biology 66 19457263
2003 Tyrosine phosphorylation of QKI mediates developmental signals to regulate mRNA metabolism. The EMBO journal 66 12682013
2020 G protein-coupled oestrogen receptor promotes cell growth of non-small cell lung cancer cells via YAP1/QKI/circNOTCH1/m6A methylated NOTCH1 signalling. Journal of cellular and molecular medicine 65 33237585
2019 QKI, a miR-200 target gene, suppresses epithelial-to-mesenchymal transition and tumor growth. International journal of cancer 65 31026342
2020 Mature myelin maintenance requires Qki to coactivate PPARβ-RXRα-mediated lipid metabolism. The Journal of clinical investigation 62 32202512
2019 miR-221 Targets QKI to Enhance the Tumorigenic Capacity of Human Colorectal Cancer Stem Cells. Cancer research 59 31416845
2014 QKI deficiency promotes FoxO1 mediated nitrosative stress and endoplasmic reticulum stress contributing to increased vulnerability to ischemic injury in diabetic heart. Journal of molecular and cellular cardiology 58 25068621
2006 QKI binds MAP1B mRNA and enhances MAP1B expression during oligodendrocyte development. Molecular biology of the cell 58 16855020
2001 Expression of QKI proteins and MAP1B identifies actively myelinating oligodendrocytes in adult rat brain. Molecular and cellular neurosciences 57 11178867
2019 MicroRNA-155 Promotes Myocardial Infarction-Induced Apoptosis by Targeting RNA-Binding Protein QKI. Oxidative medicine and cellular longevity 56 31191799
2007 The selective RNA-binding protein quaking I (QKI) is necessary and sufficient for promoting oligodendroglia differentiation. The Journal of biological chemistry 54 17575274
1998 QKI expression is regulated during neuron-glial cell fate decisions. Journal of neuroscience research 51 9778149
2020 Targeting QKI-7 in vivo restores endothelial cell function in diabetes. Nature communications 49 32732889
2019 A regulatory circuit of circ-MTO1/miR-17/QKI-5 inhibits the proliferation of lung adenocarcinoma. Cancer biology & therapy 46 30975029
2011 The QKI-PLP pathway controls SIRT2 abundance in CNS myelin. Glia 45 21948283
2006 Rescuing qkV dysmyelination by a single isoform of the selective RNA-binding protein QKI. The Journal of neuroscience : the official journal of the Society for Neuroscience 45 17079655
2011 RNA binding protein QKI inhibits the ischemia/reperfusion-induced apoptosis in neonatal cardiomyocytes. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 44 22178871
2021 QKI-5 regulates the alternative splicing of cytoskeletal gene ADD3 in lung cancer. Journal of molecular cell biology 41 33196842
2023 The RNA-binding protein QKI governs a muscle-specific alternative splicing program that shapes the contractile function of cardiomyocytes. Cardiovascular research 39 36627242
2016 RNA-binding protein QKI-5 inhibits the proliferation of clear cell renal cell carcinoma via post-transcriptional stabilization of RASA1 mRNA. Cell cycle (Georgetown, Tex.) 39 27767378
2009 The QKI-6 and QKI-7 RNA binding proteins block proliferation and promote Schwann cell myelination. PloS one 39 19517016
2021 Qki activates Srebp2-mediated cholesterol biosynthesis for maintenance of eye lens transparency. Nature communications 38 34021134
2013 Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells. Oncology reports 38 24398626
2016 MicroRNA-214 Promotes Dendritic Development by Targeting the Schizophrenia-associated Gene Quaking (Qki). The Journal of biological chemistry 35 27129236
2020 Targeting the radiation-induced TR4 nuclear receptor-mediated QKI/circZEB1/miR-141-3p/ZEB1 signaling increases prostate cancer radiosensitivity. Cancer letters 34 32768524
2016 The STAR protein QKI-7 recruits PAPD4 to regulate post-transcriptional polyadenylation of target mRNAs. Nucleic acids research 34 26926106
2014 QKI-5 suppresses cyclin D1 expression and proliferation of oral squamous cell carcinoma cells via MAPK signalling pathway. International journal of oral and maxillofacial surgery 34 25457822
2010 The QKI-6 RNA binding protein regulates actin-interacting protein-1 mRNA stability during oligodendrocyte differentiation. Molecular biology of the cell 34 20631256
2008 Essential function, sophisticated regulation and pathological impact of the selective RNA-binding protein QKI in CNS myelin development. Future neurology 34 19727426
2019 The RNA-binding protein QKI controls alternative splicing in vascular cells, producing an effective model for therapy. Journal of cell science 32 31331967
2019 SIRT1 mediates the role of RNA-binding protein QKI 5 in the synthesis of triglycerides in non-alcoholic fatty liver disease mice via the PPARα/FoxO1 signaling pathway. International journal of molecular medicine 31 30664220
2003 The quakingviable mutation affects qkI mRNA expression specifically in myelin-producing cells of the nervous system. Nucleic acids research 31 12888522
2021 Circ-SHPRH suppresses cadmium-induced transformation of human bronchial epithelial cells by regulating QKI expression via miR-224-5p. Ecotoxicology and environmental safety 30 34082244
2010 Haploinsufficiency of the gene Quaking (QKI) is associated with the 6q terminal deletion syndrome. American journal of medical genetics. Part A 30 20082458
2021 Single cell RNA sequencing identifies IGFBP5 and QKI as ciliated epithelial cell genes associated with severe COPD. Respiratory research 29 33823868
2010 The QKI-6 RNA binding protein localizes with the MBP mRNAs in stress granules of glial cells. PloS one 29 20862255
2021 Qki is an essential regulator of microglial phagocytosis in demyelination. The Journal of experimental medicine 28 33045062
2020 QKI deficiency leads to osteoporosis by promoting RANKL-induced osteoclastogenesis and disrupting bone metabolism. Cell death & disease 28 32382069
2010 The star family member QKI and cell signaling. Advances in experimental medicine and biology 28 21189683
2019 QKI-6 inhibits bladder cancer malignant behaviours through down-regulating E2F3 and NF-κB signalling. Journal of cellular and molecular medicine 27 31449345
2019 A long noncoding RNA binding to QKI-5 regulates germ cell apoptosis via p38 MAPK signaling pathway. Cell death & disease 27 31541077
2019 QKI regulates adipose tissue metabolism by acting as a brake on thermogenesis and promoting obesity. EMBO reports 27 31868295
2017 MicroRNA-214 regulates smooth muscle cell differentiation from stem cells by targeting RNA-binding protein QKI. Oncotarget 27 28186995
2017 Transcriptome profiling of mouse brains with qkI-deficient oligodendrocytes reveals major alternative splicing defects including self-splicing. Scientific reports 27 28790308
2014 QKI impairs self-renewal and tumorigenicity of oral cancer cells via repression of SOX2. Cancer biology & therapy 27 24918581
2011 E2F1 and RNA binding protein QKI comprise a negative feedback in the cell cycle regulation. Cell cycle (Georgetown, Tex.) 27 21768773
2021 Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis. eLife 26 33942715
2021 The Emerging Roles of the RNA Binding Protein QKI in Cardiovascular Development and Function. Frontiers in cell and developmental biology 26 34222237
2019 The RNA-binding protein QKI-7 recruits the poly(A) polymerase GLD-2 for 3' adenylation and selective stabilization of microRNA-122. The Journal of biological chemistry 26 31792053
2017 Extracellular vesicles-mediated transfer of miR-208a/b exaggerate hypoxia/reoxygenation injury in cardiomyocytes by reducing QKI expression. Molecular and cellular biochemistry 26 28283792
2020 Salidroside Attenuates Doxorubicin-Induced Cardiac Dysfunction Partially Through Activation of QKI/FoxO1 Pathway. Journal of cardiovascular translational research 24 32671648
2017 NF-κB-regulated miR-155, via repression of QKI, contributes to the acquisition of CSC-like phenotype during the neoplastic transformation of hepatic cells induced by arsenite. Molecular carcinogenesis 23 29240254
2020 MiR-362-5p, Which Is Regulated by Long Non-Coding RNA MBNL1-AS1, Promotes the Cell Proliferation and Tumor Growth of Bladder Cancer by Targeting QKI. Frontiers in pharmacology 22 32194406
2010 STAR trek: An introduction to STAR family proteins and review of quaking (QKI). Advances in experimental medicine and biology 22 21189682
2021 RNA-binding protein QKI suppresses breast cancer via RASA1/MAPK signaling pathway. Annals of translational medicine 18 33569406
2019 QKI deficiency maintains glioma stem cell stemness by activating the SHH/GLI1 signaling pathway. Cellular oncology (Dordrecht, Netherlands) 16 31292920
2019 Inhibition of miR-574-5p suppresses cell growth and metastasis and enhances chemosensitivity by targeting RNA binding protein QKI in cervical cancer cells. Naunyn-Schmiedeberg's archives of pharmacology 16 31786621
2021 Matrix stiffening induces a pathogenic QKI-miR-7-SRSF1 signaling axis in pulmonary arterial endothelial cells. American journal of physiology. Lung cellular and molecular physiology 15 33565360
2015 miR-29a promotes scavenger receptor A expression by targeting QKI (quaking) during monocyte-macrophage differentiation. Biochemical and biophysical research communications 15 26056009
2022 LncRNA CCAT1 enhances chemoresistance in hepatocellular carcinoma by targeting QKI-5. Scientific reports 14 35552451
2020 The RNA-binding protein QKI suppresses tumorigenesis of clear cell renal cell carcinoma by regulating the expression of HIF-1α. Journal of Cancer 14 32047543
2019 RNA-binding protein QKI regulates contact inhibition via Yes-associate protein in ccRCC. Acta biochimica et biophysica Sinica 14 30566575
2024 Isoform balance of the long noncoding RNA NEAT1 is regulated by the RNA-binding protein QKI, governs the glioma transcriptome, and impacts cell migration. The Journal of biological chemistry 13 39032650
2024 Mature microRNA-binding protein QKI promotes microRNA-mediated gene silencing. RNA biology 12 38372062
2023 MYB/MYBL1::QKI fusion-positive diffuse glioma. Journal of neuropathology and experimental neurology 12 36592415
2022 Muscle stem cell polarity requires QKI-mediated alternative splicing of Integrin Alpha-7 (Itga7). Life science alliance 12 35165120
2019 Effects of RNA binding protein QKI on pancreatic cancer ductal epithelial cells and surrounding activation fibroblasts. Journal of cellular biochemistry 12 30968977
1998 Four isoforms of the signal-transduction and RNA-binding protein QKI expressed during chicken spermatogenesis. Molecular reproduction and development 12 9547512
2024 GAS5 regulated by FTO-mediated m6A modification suppresses cell proliferation via the IGF2BP2/QKI axis in breast cancer. Discover oncology 11 38782769
2022 QKI-6 Suppresses Cell Proliferation, Migration, and EMT in Non-Small Cell Lung Cancer. Frontiers in oncology 11 35600368
2021 Loss of QKI in macrophage aggravates inflammatory bowel disease through amplified ROS signaling and microbiota disproportion. Cell death discovery 11 33758177
2021 QKI 6 ameliorates CIRI through promoting synthesis of triglyceride in neuron and inhibiting neuronal apoptosis associated with SIRT1-PPARγ-PGC-1α axis. Brain and behavior 11 34227244
2019 Spinal Pleomorphic Xanthoastrocytoma With a QKI-RAF1 Fusion. Journal of neuropathology and experimental neurology 11 30517658
2019 QKI-V5 is downregulated in CNS inflammatory demyelinating diseases. Multiple sclerosis and related disorders 11 31835207
2022 miR-31/QKI-5 axis facilitates cell cycle progression of non-small-cell lung cancer cells by interacting and regulating p21 and CDK4/6 expressions. Cancer medicine 9 36172919
2016 Characterization and Expression of the Zebrafish qki Paralogs. PloS one 9 26727370
2010 QKI-7 regulates expression of interferon-related genes in human astrocyte glioma cells. PloS one 9 20927331
2024 circPRMT10 regulated by QKI hypermethylation attenuates lung tumorigenesis induced by tobacco carcinogen NNK. Journal of hazardous materials 8 39694006
2021 QKI-Regulated Alternative Splicing Events in Cervical Cancer: Pivotal Mechanism and Potential Therapeutic Strategy. DNA and cell biology 8 34551268
2023 RNA-binding Protein QKI Inhibits Osteogenic Differentiation Via Suppressing Wnt Pathway. Archives of medical research 7 37460362
2020 MYB-QKI rearrangement in angiocentric glioma. Clinical neuropathology 7 32589128
2020 Targeting the RNA-Binding Protein QKI in Myeloid Cells Ameliorates Macrophage-Induced Renal Interstitial Fibrosis. Epigenomes 7 34968236

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