Affinage

SYNCRIP

Heterogeneous nuclear ribonucleoprotein Q · UniProt O60506

Length
623 aa
Mass
69.6 kDa
Annotated
2026-06-10
59 papers in source corpus 47 papers cited in narrative 46 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

SYNCRIP (hnRNP Q/NSAP1/GRY-RBP) is a multifunctional cytoplasmic RNA-binding protein that controls the post-transcriptional fate of selected mRNAs and miRNAs through sequence-specific binding, governing translation, mRNA stability, RNA sorting, and RNP granule dynamics (PMID:10734137, PMID:29483512). Its modular architecture couples an N-terminal cryptic RNA-binding domain (NURR) that recognizes a short hEXO sequence to canonical RRM domains that read flanking sequence, an arrangement required for high-affinity miRNA binding and for selective sorting of miRNAs into exosomes/extracellular vesicles—a function antagonized by PCBP2 (PMID:29483512, PMID:27732855, PMID:40601477). A major role of SYNCRIP is as an IRES trans-acting factor and translational regulator: it directly binds 5'UTR IRES or regulatory elements to tune translation of clock and stress mRNAs (AANAT, Per1, Rev-erbα, Bmal1, Cry1), BiP, p53, and FMRP, often in a rhythmic or stimulus-dependent manner (PMID:17403780, PMID:17074807, PMID:20576698, PMID:30948510, PMID:22935615, PMID:30478144), while isoform hnRNP-Q2 competes with PABP at poly(A) tails to broadly suppress cap- and IRES-dependent translation (PMID:23700384). SYNCRIP also stabilizes target transcripts through 3'UTR binding (Nox2, VRK2, Ccr2, prospero) and promotes neuronal pro-neural mRNA stability via iCLIP-defined targets and cooperation with miR-9 (PMID:24844655, PMID:30488434, PMID:39244479, PMID:32205310, PMID:33030396). In neurons it localizes to microtubule-dependent dendritic transport granules with Staufen1 and regulates morphogenesis by localizing Cdc42/N-WASP/Arp2/3 pathway mRNAs (PMID:15475564, PMID:22493061), and its Drosophila ortholog directs localization and translation of oskar/gurken and synaptic mRNAs at the NMJ (PMID:23213441, PMID:25171822, PMID:32040548). Beyond translation, SYNCRIP modulates SMN2 exon 7 splicing in an isoform-specific manner and participates in let-7a biogenesis via the microprocessor (PMID:18794368, PMID:31907208), suppresses apoB and APOBEC3B-driven C-to-U/cytidine deaminase activity (PMID:11134005, PMID:11352648, PMID:37478850), and supports HCV and MHV viral RNA replication (PMID:19232660, PMID:21715376, PMID:15542667). At the cellular-systems level, SYNCRIP is required for myeloid leukemia stem cell maintenance through HOXA9 translation, hematopoietic stem cell proteostasis through CDC42 translation, and cortical neurogenesis through phase-separation–dependent mRNA stabilization complexes, with pathogenic human mutations weakening this phase-separation capacity (PMID:28436985, PMID:37085479, PMID:39776340).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2000 High

    Established SYNCRIP as a distinct cytoplasmic poly(A) RNA-binding protein, distinguishing it from its nuclear paralog and linking it to synaptotagmin-associated machinery.

    Evidence Co-IP, in vitro binding, and fractionation in COS cells; identification as an apoB editosome component binding APOBEC1/ACF

    PMID:10734137 PMID:11134005 PMID:11352648

    Open questions at the time
    • Functional consequence of synaptotagmin interaction not resolved
    • Mechanism of editing suppression beyond competition not detailed
  2. 2002 Medium

    Placed SYNCRIP in the SMN/motor-neuron RNA-processing pathway and showed insulin-signaling-coupled phosphoregulation of its RNA metabolism functions.

    Evidence Yeast two-hybrid with SMA mutant SMN forms; MALDI-MS identification of tyrosine-phosphorylated pp68 and in vitro insulin receptor kinase assay

    PMID:11773003 PMID:11994298

    Open questions at the time
    • SMN interaction not confirmed by reciprocal Co-IP in mammalian cells at this stage
    • In vivo relevance of insulin-receptor phosphorylation untested
  3. 2004 High

    Demonstrated SYNCRIP is a motile component of dendritic mRNA transport granules, defining a role in spatial mRNA delivery in neurons.

    Evidence Live imaging of FP-tagged granules with nocodazole inhibition and co-transport with Staufen1 and IP3R1 3'UTR in hippocampal neurons

    PMID:15475564

    Open questions at the time
    • Cargo selectivity rules not defined
    • Link between transport and local translation not established here
  4. 2006 High

    Defined SYNCRIP as an IRES trans-acting factor and arginine-methylation substrate, explaining both a translational activity and the control of its nucleocytoplasmic distribution.

    Evidence BiP IRES reporter/polysome assays under heat stress; PRMT1 in vitro methylation with Adox-induced cytoplasmic redistribution

    PMID:16765914 PMID:17010310 PMID:17074807

    Open questions at the time
    • How methylation status switches between functions in vivo unclear
    • Generality of IRES enhancement across mRNAs not yet shown
  5. 2007 High

    Extended SYNCRIP's RNA targets to noncoding dendritic regulatory RNAs and rhythmic translation of melatonin biosynthesis.

    Evidence Domain-mapped in vitro binding and human brain IP for BC200; IRES reporter/RIP/melatonin assays for AANAT in pinealocytes

    PMID:17403780 PMID:18045242

    Open questions at the time
    • Functional role of BC200 binding in transport not demonstrated
    • Upstream signal driving rhythmic AANAT binding not identified
  6. 2008 High

    Showed isoform-specific, position-dependent control of alternative splicing, identifying SYNCRIP as an SMN2 exon 7 splicing modulator.

    Evidence Affinity chromatography, isoform overexpression/depletion, and RT-PCR splicing assays mapping binding near exon 7 +6

    PMID:18794368

    Open questions at the time
    • Mechanism by which Q2/Q3 antagonize Q1 unresolved
    • Nuclear vs cytoplasmic isoform distribution not integrated
  7. 2009 High

    Identified SYNCRIP as a positive host factor for viral RNA replication and a stress-responsive granule component.

    Evidence siRNA knockdown and in vitro immunodepletion replication assays for HCV; stress-induced relocalization to BiP/TIA-1 granules by immunofluorescence

    PMID:19232660 PMID:19331829

    Open questions at the time
    • Direct role of SYNCRIP in the replication complex vs IRES translation not fully separated
    • Functional consequence of stress-granule localization untied to phenotype
  8. 2011 High

    Provided mechanistic detail of SYNCRIP positioning mRNA on the 40S ribosome and extended rhythmic IRES regulation to a second clock gene.

    Evidence In vitro ribosome assembly/toeprinting on HCV IRES; mPer1 IRES reporter/RIP/knockdown

    PMID:21715376 PMID:22124155

    Open questions at the time
    • Identity of the contacted 40S ribosomal protein not fully characterized
    • How phase-dependent binding is timed not resolved
  9. 2012 High

    Connected SYNCRIP to cell-fate decisions and cytoskeletal mRNA localization across translation control, neuronal morphogenesis, and oocyte axis specification.

    Evidence p53 5'UTR translation assays; shRNA + RIP + dominant-negative rescue mapping Cdc42/N-WASP/Arp2/3 mRNA localization; Drosophila syncrip genetics on grk/osk

    PMID:22493061 PMID:22935615 PMID:23213441

    Open questions at the time
    • Whether morphogenesis effect is via transport vs translation not separated
    • Conservation of axis-specification mechanism in mammals unknown
  10. 2013 High

    Defined a global translational repressor mode in which SYNCRIP competes with PABP at poly(A) tails and at specific 3'UTR elements.

    Evidence In vitro reconstitution of 48S/80S assembly with PABP competition; YB-1 3'UTR pulldown and translation assays

    PMID:23700384 PMID:23980891

    Open questions at the time
    • Determinants selecting global vs target-specific repression unclear
    • Isoform usage governing the switch not defined
  11. 2014 High

    Established 3'UTR-mediated mRNA stabilization (Nox2) and an in vivo synaptic/translational role at the Drosophila NMJ.

    Evidence mRNA pulldown/MS and ROS assays for Nox2; RIP-seq and genetic null analysis of synaptic mRNAs and BMP signaling at the NMJ

    PMID:24844655 PMID:25171822 PMID:25171887

    Open questions at the time
    • How SYNCRIP toggles between stabilizing and destabilizing outcomes unresolved
    • Direct vs indirect control of BMP ligand levels not dissected
  12. 2016 High

    Discovered hEXO-motif–based selective sorting of miRNAs into exosomes and extended IRES/translational control to additional clock genes.

    Evidence shRNA/RIP/miRNA profiling and hEXO motif mutagenesis in hepatocytes; NMR of the N-terminal acidic domain; mCry1 5'UTR translation assays

    PMID:27081926 PMID:27392095 PMID:27732855

    Open questions at the time
    • Structural basis of hEXO recognition not yet solved at this point
    • How sorting integrates with translational roles unclear
  13. 2017 High

    Identified SYNCRIP as a requirement for myeloid leukemia stem cell maintenance via HOXA9 translation within an MSI2-shared target network.

    Evidence MSI2 interactome proteomics, shRNA screen, in vivo leukemia model, and MSI2/HOXA9 rescue

    PMID:28436985

    Open questions at the time
    • Direct vs indirect MSI2 relationship not fully resolved
    • Mechanism of HOXA9 translational control not detailed
  14. 2018 High

    Solved how the NURR domain combines with RRMs to achieve sequence-specific miRNA recognition and exosomal partitioning.

    Evidence Crystallographic/NMR structural analysis with mutagenesis and functional partitioning assays

    PMID:29483512

    Open questions at the time
    • In vivo regulation of NURR-RRM coupling unknown
    • Full repertoire of hEXO-bearing targets not defined
  15. 2019 High

    Consolidated SYNCRIP's neuronal functions—SMA rescue, axon-guidance-coupled FMRP translation, mRNA stability control of proteostasis, and circadian Bmal1 translation.

    Evidence Co-IP/RNA-seq/motif analysis and in vivo SMA rescue across models; fmr1 IRES reporter under Sema3A; VRK2 3'UTR stability assays; Bmal1 5'UTR rhythmic translation

    PMID:30478144 PMID:30488434 PMID:30649277 PMID:30948510

    Open questions at the time
    • Therapeutic window of SYNCRIP overexpression in SMA untested here
    • Coordination across these neuronal targets not integrated
  16. 2020 High

    Expanded SYNCRIP into miRNA biogenesis and genome-wide neuronal RNA regulation alongside activity-dependent synaptic translation.

    Evidence Co-IP with Drosha/DGCR8 and domain-mapped pri-let-7a loop binding; iCLIP neuronal interactome with miR-9 cooperation; single-molecule imaging of msp300:Syp:eIF4E granules; prospero long-3'UTR stabilization

    PMID:31907208 PMID:32040548 PMID:32205310 PMID:33030396

    Open questions at the time
    • How SYNCRIP couples microprocessor activity to its other roles unclear
    • Rules distinguishing stabilized vs repressed iCLIP targets undefined
  17. 2021 Medium

    Defined competitive translational regulation with hnRNP A1 at the Cfl1 5'UTR linking SYNCRIP localization to ischemic cytoskeletal pathology.

    Evidence RNA pulldown competition and in vitro translation under oxygen-glucose deprivation

    PMID:34944075

    Open questions at the time
    • RNA binding competition and translation assay from a single lab/study
    • Trigger relocalizing hnRNP Q under OGD not defined
  18. 2023 High

    Revealed SYNCRIP as a tumor-suppressive restraint on APOBEC3B mutagenesis and an essential factor for hematopoietic stem cell proteostasis via CDC42 translation.

    Evidence SYNCRIP knockout + genomic/mutational signature analysis in prostate cancer; conditional KO mouse with polysome profiling, proteomics, and CDC42 rescue in HSCs

    PMID:37085479 PMID:37478850

    Open questions at the time
    • Mechanism by which SYNCRIP loss activates APOBEC3B not detailed
    • How proteostasis and translation control are mechanistically linked unclear
  19. 2024 High

    Extended SYNCRIP's 3'UTR-stabilization function to nociceptive signaling and showed RNA-dependent partnership with LIN28B in the let-7 axis.

    Evidence siRNA/AAV bidirectional manipulation with Ccr2 3'UTR binding and pain behavior; RNA-dependent Co-IP with LIN28B and let-7/TRIM71 readouts in HCC cells

    PMID:38976670 PMID:39244479

    Open questions at the time
    • Direct vs indirect LIN28B interaction mechanism unresolved
    • Whether Ccr2 stabilization uses the same machinery as other 3'UTR targets unknown
  20. 2025 Medium

    Established PCBP2 as a dominant antagonist of SYNCRIP-mediated EV miRNA loading and tied phase-separation–dependent mRNA stabilization complexes to cortical neurogenesis and human disease mutations.

    Evidence CLIP/EMSA/mutagenesis with EV miRNA profiling showing PCBP2 requires SYNCRIP; conditional KO + scRNA-seq + phase-separation assays linking SYNCRIP mutations to Notch-dependent radial glial fate

    PMID:39776340 PMID:40601477

    Open questions at the time
    • How PCBP2 converts SYNCRIP-bound miRNAs to retained pool not fully resolved
    • Molecular composition of phase-separated stabilization complex undefined
  21. 2026 Medium

    Positioned SYNCRIP as a late-phase stress granule disassembly factor, integrating its RNP-granule biology with stress recovery.

    Evidence Time-resolved G3BP1 proximity proteomics and siRNA knockdown with stress granule imaging

    PMID:42061552

    Open questions at the time
    • Proximity proteomics + knockdown from single study
    • Molecular mechanism of granule clearance not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how SYNCRIP's isoform identity, arginine methylation, phosphorylation, and phase-separation collectively switch it between translational activation, repression, mRNA stabilization, splicing, and miRNA sorting on specific targets.
  • No unified model linking post-translational modifications to functional mode-switching
  • Determinants of target selection across competing functions undefined
  • In vivo coordination of cytoplasmic vs nuclear roles unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 12 GO:0045182 translation regulator activity 9 GO:0098772 molecular function regulator activity 5 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0005829 cytosol 5 GO:0031410 cytoplasmic vesicle 3 GO:0005634 nucleus 2
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-8953854 Metabolism of RNA 5 R-HSA-9909396 Circadian clock 5 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1643685 Disease 2
Partners
APOBEC1LIN28BMSI2PABPPCBP2PRMT1SMNSTAUFEN1
Complex memberships
Microprocessor (Drosha/DGCR8)apoB mRNA editosomeexosomal miRNA sorting machinerymRNA transport granule

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 SYNCRIP was identified as a cytoplasmic RNA-binding protein that interacts with ubiquitous synaptotagmin isoforms (Syt-VII, Syt-VIII, Syt-IX) through their C2B domains, as shown by in vitro binding experiments and co-immunoprecipitation in COS cells. SYNCRIP binds poly(A) RNA and localizes predominantly to the cytoplasm in contrast to the nuclear localization of its paralog hnRNP R. Co-immunoprecipitation, in vitro binding assays, biochemical fractionation, immunohistochemistry The Journal of biological chemistry Medium 10734137
2000 GRY-RBP (SYNCRIP) was identified as a component of the apoB mRNA editosome; it binds to APOBEC1 and ACF, and also binds apoB RNA directly. GRY-RBP competitively inhibits ACF binding to apoB RNA and suppresses C-to-U RNA editing; antisense knockdown in rat hepatoma cells increased apoB C-to-U editing. Yeast two-hybrid, recombinant protein binding assays, antisense knockdown, immunofluorescence co-localization The Journal of biological chemistry High 11134005 11352648
2002 SYNCRIP (gry-rbp/hnRNP-Q) physically interacts with SMN (survival motor neuron protein) via yeast two-hybrid and the interaction is lost with truncated or SMA-associated mutant SMN forms, placing SYNCRIP in the SMN pathway relevant to motor neuron RNA processing. Yeast two-hybrid Human molecular genetics Medium 11773003
2002 SYNCRIP/NSAP1 was identified as a tyrosine-phosphorylated protein (pp68) in adipocytes; it associates with free polysomes in low-density microsomes, and RNA binding to SYNCRIP specifically inhibits its in vitro phosphorylation by the insulin receptor, suggesting regulation of mRNA metabolism by insulin signaling. MALDI mass spectrometry, subcellular fractionation, in vitro kinase assay The Journal of biological chemistry Medium 11994298
2004 SYNCRIP is a component of mRNA transport granules in rat hippocampal neuron dendrites; fluorescent protein-tagged SYNCRIP granules move bi-directionally in dendrites at ~0.05 μm/s in a microtubule-dependent manner (inhibited by nocodazole), and SYNCRIP co-transports with Staufen1 and the IP3R1 mRNA 3'UTR. Time-lapse live imaging, pharmacological inhibition (nocodazole), co-immunoprecipitation, fluorescence co-localization The Journal of biological chemistry High 15475564
2004 SYNCRIP binds both positive- and negative-strand 5' UTR leader sequences (UCUAA repeat) of mouse hepatitis virus (MHV) RNA; overexpression or siRNA knockdown of SYNCRIP modulates MHV RNA synthesis (knockdown delays synthesis), identifying SYNCRIP as a positive regulator of MHV RNA replication without affecting viral translation. UV cross-linking, RNA affinity purification, MALDI-MS, siRNA knockdown, in vivo/in vitro binding Journal of virology Medium 15542667
2006 NSAP1 (SYNCRIP) enhances BiP IRES-mediated translation by directly binding the IRES element; NSAP1 binding to the BiP IRES increases under heat stress, and knockdown by siRNA reduces BiP IRES activity and shifts BiP mRNA from heavy to light polysomes. siRNA knockdown, luciferase reporter assay, polysome fractionation, RNA-protein binding assay Molecular and cellular biology High 17074807
2006 hnRNPQ3 (NSAP1/SYNCRIP) is a substrate for PRMT1-mediated arginine methylation at its C-terminal RGG box domain; methylation is required for nuclear localization, as inhibition of methylation with Adox causes redistribution of hnRNP Q from nucleus to cytoplasm. Yeast two-hybrid, in vitro methylation assay, Adox inhibitor treatment, immunofluorescence Biochemical and biophysical research communications Medium 16765914
2006 The N-terminal acidic domain (AcD) of hnRNPQ (SYNCRIP) directly interacts with APOBEC1 via in vitro pull-down; this interaction is regulated by phosphorylation of AcD by protein kinase C, which induces conformational changes confirmed by NMR spectroscopy and mass spectrometry. In vitro pull-down, NMR structural modeling, in vitro phosphorylation, mass spectrometry Biochemical and biophysical research communications Medium 17010310
2007 SYNCRIP directly binds BC200 RNA (a dendritic translational regulator) via its N-terminal RNA recognition motifs and the internal A-rich region of BC200 RNA; SYNCRIP associates with BC200 RNA in vivo in human brain as shown by immunoprecipitation, and may recruit BC200 RNA into neuronal mRNA transport complexes. In vitro binding assay, immunoprecipitation from human brain Journal of neurochemistry Medium 18045242
2007 hnRNP Q (SYNCRIP) acts as an IRES trans-acting factor (ITAF) for rhythmic translation of AANAT mRNA via a conserved 5'UTR IRES element, with peak binding at night; hnRNP Q knockdown in pinealocytes reduces peak AANAT protein amplitude and melatonin production without affecting mRNA levels. siRNA knockdown, IRES reporter assay, RNA immunoprecipitation, melatonin measurement Genes & development High 17403780
2008 hnRNP Q1 (major isoform of SYNCRIP) directly binds SMN2 exon 7 near nucleotide +6 and promotes exon 7 inclusion in SMN2 splicing, while minor isoforms Q2/Q3 antagonize Q1 and promote exon skipping; depletion of all three isoforms also enhances exon 7 inclusion, demonstrating isoform-specific splicing modulation. Affinity chromatography, RNA binding assay, overexpression, siRNA depletion, RT-PCR splicing assay Molecular and cellular biology High 18794368
2009 SYNCRIP associates with detergent-resistant membrane fractions and co-localizes with newly synthesized HCV RNA; siRNA knockdown significantly decreases HCV RNA levels in replicon cells, and immunodepletion of SYNCRIP impairs in vitro HCV RNA replication, identifying SYNCRIP as a direct positive regulator of HCV RNA replication in addition to its previously reported role in IRES-mediated translation. siRNA knockdown, subcellular fractionation, in vitro replication assay, immunodepletion Virology High 19232660
2009 Under stress conditions (PMA, thapsigargin, arsenite, heat shock), hnRNP Q (normally predominantly nuclear) re-localizes to cytoplasmic granules where it co-localizes with the ER chaperone BiP, and partially with stress granule marker TIA-1. Immunofluorescence, stress treatment, co-localization analysis Experimental cell research Medium 19331829
2010 hnRNP Q (SYNCRIP) and PTB modulate IRES-mediated translation of Rev-erbα clock protein; hnRNP Q rhythmically binds the Rev-erbα 5'UTR IRES, and this rhythmic binding affinity combined with changes in PTB cytosolic levels maintains Rev-erbα protein oscillation. IRES reporter assay, RNA binding assay, siRNA knockdown, co-immunoprecipitation Nucleic acids research Medium 20576698
2011 NSAP1 (SYNCRIP) facilitates formation of translation-competent 48S ribosome-mRNA complex on HCV IRES by positioning HCV mRNA on the 40S ribosomal subunit; NSAP1 associates with the solvent side of the 40S subunit and directly binds a specific site downstream of the initiation codon and a 40S ribosomal protein. Ribosome assembly assay, toeprinting, RNA-protein binding, sucrose gradient sedimentation Nucleic acids research High 21715376
2011 mhnRNP Q (SYNCRIP) acts as an ITAF for IRES-mediated translation of mPer1 mRNA; hnRNP Q rhythmically binds the mPer1 5'UTR IRES in a phase-dependent manner, and knockdown of hnRNP Q decreases mPER1 protein levels and slightly delays its expression without affecting mRNA levels. IRES reporter assay, RNA immunoprecipitation, siRNA knockdown, immunoblotting Molecular and cellular biology Medium 22124155
2012 hnRNP Q (SYNCRIP) binds the 5'UTR of mouse p53 mRNA and regulates translation efficiency; changes in cytosolic hnRNP Q levels contribute to cell cycle-dependent translational differences in p53 mRNA, with hnRNP Q knockdown or overexpression altering p53 protein levels and affecting apoptosis progression. RNA binding assay, IRES reporter assay, siRNA knockdown, overexpression, immunoblotting Cell death and differentiation Medium 22935615
2012 hnRNP Q1 (SYNCRIP) regulates neuronal morphogenesis by binding and localizing mRNAs encoding components of the Cdc42/N-WASP/Arp2/3 actin nucleation complex in neurites; knockdown of hnRNP Q increases neurite complexity and filopodium formation, reduces Cdc42 pathway mRNAs in neurites, and this phenotype is rescued by dominant-negative Cdc42 or N-WASP mutants. shRNA knockdown, immunofluorescence, subcellular fractionation, RNA immunoprecipitation, dominant-negative rescue Molecular and cellular biology High 22493061
2012 Drosophila Syncrip (ortholog of SYNCRIP) specifically binds gurken and oskar but not bicoid mRNAs; loss-of-function and overexpression of syncrip in egg chambers show it is required for correct grk and osk mRNA localization and translational regulation, identifying Syncrip as a new factor in oocyte axis specification. RNA chromatography, genetic loss-of-function/overexpression, RNA localization assay (in situ hybridization) Biology open High 23213441
2013 hnRNP-Q2 (SYNCRIP isoform 2) competes with PABP for binding to poly(A) RNA; when bound, it displaces PABP, impairs eIF4E association with the 5' cap, and inhibits 48S and 80S ribosome complex formation, thereby suppressing global cap-dependent and IRES-mediated translation in a poly(A)-dependent manner. hnRNP-Q2 also impedes let-7a miRNA-mediated deadenylation of target mRNAs. In vitro translation assay, ribosome complex analysis, poly(A) binding competition assay, siRNA depletion, recombinant protein reconstitution PLoS biology High 23700384
2013 hnRNP Q specifically interacts with the regulatory element (RE) in the YB-1 mRNA 3'UTR and inhibits its translation; hnRNP Q binding displaces PABP (a positive regulator) from the RE and increases binding of YB-1 protein (a negative regulator) to the same element. RNA pulldown, in vitro translation assay, competition binding assay Biochemistry. Biokhimiia Medium 23980891
2014 Drosophila Syncrip associates with mRNAs encoding synaptic proteins (msp-300, syd-1, neurexin-1, futsch, highwire, discs large, α-spectrin) via RNA-immunoprecipitation sequencing at the neuromuscular junction; loss of syncrip reduces MSP-300 and Discs large protein levels and causes muscle nuclear distribution defects characteristic of msp-300 mutants, demonstrating a role in translational regulation of synaptic plasticity genes. RNA immunoprecipitation followed by high-throughput sequencing (RIP-seq), qRT-PCR, genetic null mutant analysis RNA (New York, N.Y.) High 25171822
2014 SYNCRIP binds to the 3'UTR of Nox2 mRNA and stabilizes it; in M2-polarized macrophages, SYNCRIP binding to Nox2 mRNA 3'UTR is attenuated, leading to Nox2 mRNA destabilization and reduced ROS production, identified by mRNA pulldown coupled to mass spectrometry. mRNA pulldown, mass spectrometry, siRNA knockdown, ROS measurement Antioxidants & redox signaling Medium 24844655
2014 Drosophila Syncrip is expressed in muscle (not motoneuron) at the NMJ and modulates retrograde BMP signaling by regulating the level of the BMP ligand Glass Bottom Boat from the post-synapse, thereby influencing pre-synaptic vesicle release efficiency and synapse structure. Genetic null mutant analysis, tissue-specific expression, immunostaining, electrophysiology Biology open Medium 25171887
2016 SYNCRIP is a component of the hepatocyte exosomal miRNA sorting machinery; SYNCRIP knockdown impairs miRNA sorting into exosomes, and SYNCRIP directly binds to specific miRNAs enriched in exosomes via a common extra-seed sequence (hEXO motif). Embedding the hEXO motif into a poorly exported miRNA enhances its exosomal loading. shRNA knockdown, RNA immunoprecipitation, miRNA profiling, mutagenesis of hEXO motif Cell reports High 27732855
2016 hnRNP Q (SYNCRIP) binds to the 5'UTR of mCry1 mRNA and suppresses its translation, leading to altered rhythmicity of the mCRY1 protein profile in circadian clock regulation. RNA binding assay, IRES reporter assay, siRNA knockdown, immunoblotting PloS one Medium 27392095
2016 The NMR structure of the SYNCRIP N-terminal acidic domain (AcD24-107) reveals an all α-helix globular fold that is fundamentally different from previously proposed models; it contains a large hydrophobic cavity and distinct charged surface areas as potential interaction epitopes, consistent with its role in protein-protein interactions with APOBEC1. NMR structure determination Protein science Medium 27081926
2017 SYNCRIP is required for myeloid leukemia stem cell maintenance; SYNCRIP depletion increases apoptosis and differentiation, delays leukemogenesis, and causes loss of HOXA9 translation. SYNCRIP and MSI2 interact indirectly through shared mRNA targets, and MSI2 or HOXA9 overexpression rescues the effects of SYNCRIP depletion. Proteomic analysis of MSI2 interactome, shRNA functional screen, gene expression profiling, in vivo leukemia model, rescue experiment Nature genetics High 28436985
2018 Syncrip's N-terminal domain is a cryptic, sequence-specific RNA-binding domain (designated NURR) that specifically recognizes the short hEXO sequence of exosomal miRNA targets; NURR is coupled by a non-canonical structural element to Syncrip's RRM domains, requiring both NURR (for hEXO recognition) and RRM domains (for 5' flanking sequence binding) for high-affinity miRNA binding and exosomal partitioning. X-ray crystallography/NMR structural analysis, mutagenesis, binding assays, functional exosomal partitioning assays Nature communications High 29483512
2019 SYNCRIP interacts with full-length SMN (but not truncated forms) and binds and modulates motor neuron transcripts including SMN itself and NRXN2 via motif 7; SYNCRIP overexpression rescues SMA motor neurons by increasing SMN and NRXN2 levels through a positive loop, and ameliorates SMN-loss-related phenotypes in C. elegans and mouse models. RNA-seq, motif enrichment analysis, co-immunoprecipitation, overexpression in SMA models (human neurons, C. elegans, mouse) Brain High 30649277
2019 hnRNP Q (SYNCRIP) acts as an IRES trans-acting factor (ITAF) for IRES-mediated fmr1 translation in neurons; semaphorin 3A (Sema3A)-induced axonal growth cone collapse triggers upregulation of hnRNP Q, which in turn promotes IRES-mediated FMRP expression. IRES reporter assay, siRNA knockdown, neuronal stimulation assay, immunoblotting Molecular and cellular biology Medium 30478144
2019 hnRNP Q (SYNCRIP) binds to the 3'UTR of VRK2 mRNA in neuronal cells and reduces its mRNA stability; reduced SYNCRIP levels in neurons lead to decreased CCT4 protein and increased polyQ protein aggregation in neuroblastoma cells and cortical neurons. RNA binding assay, mRNA stability assay, siRNA knockdown, immunoblotting, polyQ aggregation assay Journal of neurochemistry Medium 30488434
2019 hnRNP Q (SYNCRIP) rhythmically binds to a specific region of the Bmal1 mRNA 5'UTR and negatively regulates its translation in a time-dependent manner; hnRNP Q knockdown increases BMAL1 protein oscillation amplitude and modulates BMAL1-regulated target gene mRNA oscillations. RNAi, luciferase reporter assay, RNA binding assay, real-time bioluminescence The Journal of biological chemistry Medium 30948510
2020 SYNCRIP promotes processing of pri-let-7a miRNA by associating with the microprocessor complex and binding specifically to the terminal loop of pri-let-7a via its RRM2-3 domains; SYNCRIP knockdown impairs and overexpression promotes let-7a maturation. Co-immunoprecipitation with Drosha/DGCR8, RNA binding assay, siRNA knockdown, miRNA profiling, luciferase reporter RNA (New York, N.Y.) High 31907208
2020 Drosophila Syncrip (Syp) binds msp300 (Nesprin-1) transcripts and is essential for activity-dependent accumulation of MSP-300 protein at postsynaptic compartments; elevated neural activity alters Syp dynamics and the number of msp300:Syp:eIF4E RNP granules at the NMJ synapse, implicating Syp in activity-dependent translational regulation. Single-molecule imaging, co-immunoprecipitation, live imaging, genetic loss-of-function The Journal of cell biology High 32040548
2020 Drosophila Syncrip binds long 3'UTR isoforms of prospero mRNA in neurons and stabilizes them, enabling upregulation of Prospero protein; neuronal-specific transcription of long prospero mRNA isoforms combined with Syncrip-mediated stabilization constitutes a regulatory module for neuron-specific gene expression. Single molecule FISH, RNA immunoprecipitation, genetic analysis, mRNA stability assay Biology open Medium 32205310
2020 SYNCRIP's cytoplasmic mRNA interactome in rat cortical neurons, identified by iCLIP, includes hundreds of target mRNAs enriched for neurogenesis and neurite outgrowth genes; SYNCRIP stabilizes pro-neural mRNAs (e.g., doublecortin/Dcx) via direct 3'UTR binding and synergizes with miR-9 to repress anti-neural mRNAs. iCLIP (individual-nucleotide resolution CLIP), RNA-seq, subcellular fractionation RNA biology Medium 33030396
2021 hnRNP Q and hnRNP A1 competitively regulate translation of Cfl1 (cofilin) mRNA; under normal conditions hnRNP Q binding to Cfl1 mRNA 5'UTR displaces hnRNP A1, suppressing translation; under oxygen-glucose deprivation, changes in localization of hnRNP Q increase hnRNP A1 binding and cofilin translation, promoting cofilin-actin aggregate formation. RNA pulldown, competition binding assay, in vitro translation, immunoblotting, fluorescence imaging Cells Medium 34944075
2023 SYNCRIP acts as an endogenous suppressor of APOBEC3B-driven mutagenesis in prostate cancer; SYNCRIP loss leads to overactivated APOBEC3B, which introduces driver mutations in FOXA1, EP300, and other genes, enabling androgen receptor-targeted therapy resistance. SYNCRIP knockout, genomic sequencing, functional screening, mutational signature analysis Cancer cell Medium 37478850
2023 SYNCRIP is required for hematopoietic stem cell (HSC) maintenance and proteostasis; SYNCRIP loss increases protein synthesis, dysregulates the epichaperome, causes misfolded protein accumulation and ER stress. SYNCRIP is required for translation of CDC42, and loss impairs polarity and asymmetric protein segregation in HSCs; forced CDC42 expression recovers polarity and replating activity. Conditional knockout mouse, polysome profiling, proteomics, immunofluorescence, transplantation assay, rescue experiment Nature communications High 37085479
2024 SYNCRIP binds to the 3'UTR of Ccr2 mRNA and stabilizes it in dorsal root ganglion neurons; SYNCRIP knockdown attenuates nerve injury-induced CCR2 upregulation and nociceptive hypersensitivity, while AAV-mediated SYNCRIP overexpression elevates CCR2 and induces neuropathic pain-like symptoms in naive mice. siRNA knockdown, AAV overexpression, RNA binding assay (3'UTR binding), behavioral pain assays, immunohistochemistry British journal of anaesthesia High 39244479
2024 hnRNP Q (SYNCRIP) interacts with LIN28B in an RNA-dependent manner and modulates the LIN28B/let-7 axis; hnRNP Q knockdown increases let-7 family miRNA levels, reduces LIN28B mRNA and its target TRIM71, and inhibits proliferation of hepatocellular carcinoma cells. Co-immunoprecipitation (RNA-dependent), siRNA knockdown, luciferase reporter assay, miRNA profiling PloS one Medium 38976670
2025 PCBP2 directly interacts with miRNAs bearing intracellular retention motifs and requires SYNCRIP for this binding (as shown by SYNCRIP knockdown abolishing PCBP2-miRNA interaction); SYNCRIP and PCBP2 can simultaneously bind miRNAs (EMSA); PCBP2 acts as a dominant inhibitor of SYNCRIP-mediated miRNA loading into extracellular vesicles. CLIP, RNA pulldown with proteomics, mutagenesis, EMSA, siRNA knockdown, EV miRNA profiling eLife High 40601477
2026 SYNCRIP is required for late-phase stress granule clearance; SYNCRIP knockdown specifically increases granule size at 50 minutes post-stress recovery without affecting stress granule formation, placing SYNCRIP as a late-phase disassembly factor in the stress granule lifecycle. Time-resolved proximity proteomics (G3BP1 bait), siRNA knockdown, stress granule quantification by imaging The international journal of biochemistry & cell biology Medium 42061552
2025 Syncrip (SYNCRIP) maintains transcription factor expression needed for late-stage cortical neurogenesis by recruiting mRNA stabilization complexes through phase separation; pathogenic human SYNCRIP mutations weaken phase-separation capability, impairing stable complex formation and disrupting Notch signaling that determines radial glial cell fate. Conditional knockout in mice, single-cell RNA sequencing, phase separation assays, behavioral tests Advanced science Medium 39776340

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 The RNA-Binding Protein SYNCRIP Is a Component of the Hepatocyte Exosomal Machinery Controlling MicroRNA Sorting. Cell reports 484 27732855
2002 Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons? Human molecular genetics 242 11773003
2018 A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets. Nature communications 104 29483512
2008 The RNA binding protein hnRNP Q modulates the utilization of exon 7 in the survival motor neuron 2 (SMN2) gene. Molecular and cellular biology 98 18794368
2004 An RNA-interacting protein, SYNCRIP (heterogeneous nuclear ribonuclear protein Q1/NSAP1) is a component of mRNA granule transported with inositol 1,4,5-trisphosphate receptor type 1 mRNA in neuronal dendrites. The Journal of biological chemistry 93 15475564
2017 Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells. Nature genetics 88 28436985
2000 Identification of GRY-RBP as an apolipoprotein B RNA-binding protein that interacts with both apobec-1 and apobec-1 complementation factor to modulate C to U editing. The Journal of biological chemistry 85 11134005
2000 SYNCRIP, a cytoplasmic counterpart of heterogeneous nuclear ribonucleoprotein R, interacts with ubiquitous synaptotagmin isoforms. The Journal of biological chemistry 83 10734137
2007 Rhythmic control of AANAT translation by hnRNP Q in circadian melatonin production. Genes & development 79 17403780
2011 Rhythmic interaction between Period1 mRNA and hnRNP Q leads to circadian time-dependent translation. Molecular and cellular biology 59 22124155
2010 hnRNP Q and PTB modulate the circadian oscillation of mouse Rev-erb alpha via IRES-mediated translation. Nucleic acids research 53 20576698
2012 hnRNP Q regulates translation of p53 in normal and stress conditions. Cell death and differentiation 51 22935615
2012 Drosophila Syncrip binds the gurken mRNA localisation signal and regulates localised transcripts during axis specification. Biology open 51 23213441
2014 The hnRNP-Q protein LIF2 participates in the plant immune response. PloS one 49 24914891
2013 Control of translation and miRNA-dependent repression by a novel poly(A) binding protein, hnRNP-Q. PLoS biology 49 23700384
2007 SYNCRIP, a component of dendritically localized mRNPs, binds to the translation regulator BC200 RNA. Journal of neurochemistry 47 18045242
2023 Loss of SYNCRIP unleashes APOBEC-driven mutagenesis, tumor heterogeneity, and AR-targeted therapy resistance in prostate cancer. Cancer cell 44 37478850
2006 BiP internal ribosomal entry site activity is controlled by heat-induced interaction of NSAP1. Molecular and cellular biology 44 17074807
2012 hnRNP Q regulates Cdc42-mediated neuronal morphogenesis. Molecular and cellular biology 43 22493061
2014 Drosophila Syncrip modulates the expression of mRNAs encoding key synaptic proteins required for morphology at the neuromuscular junction. RNA (New York, N.Y.) 40 25171822
2004 SYNCRIP, a member of the heterogeneous nuclear ribonucleoprotein family, is involved in mouse hepatitis virus RNA synthesis. Journal of virology 38 15542667
2019 Key role of SMN/SYNCRIP and RNA-Motif 7 in spinal muscular atrophy: RNA-Seq and motif analysis of human motor neurons. Brain : a journal of neurology 37 30649277
2001 Two-hybrid cloning identifies an RNA-binding protein, GRY-RBP, as a component of apobec-1 editosome. Biochemical and biophysical research communications 35 11352648
2014 SYNCRIP-dependent Nox2 mRNA destabilization impairs ROS formation in M2-polarized macrophages. Antioxidants & redox signaling 32 24844655
2009 SYNCRIP (synaptotagmin-binding, cytoplasmic RNA-interacting protein) is a host factor involved in hepatitis C virus RNA replication. Virology 32 19232660
2006 The methylation of the C-terminal region of hnRNPQ (NSAP1) is important for its nuclear localization. Biochemical and biophysical research communications 31 16765914
2009 Human hnRNP Q re-localizes to cytoplasmic granules upon PMA, thapsigargin, arsenite and heat-shock treatments. Experimental cell research 29 19331829
2002 Identification of pp68 as the Tyrosine-phosphorylated Form of SYNCRIP/NSAP1. A cytoplasmic RNA-binding protein. The Journal of biological chemistry 29 11994298
2014 Syncrip/hnRNP Q influences synaptic transmission and regulates BMP signaling at the Drosophila neuromuscular synapse. Biology open 26 25171887
2011 Translation-competent 48S complex formation on HCV IRES requires the RNA-binding protein NSAP1. Nucleic acids research 24 21715376
2020 Syncrip/hnRNP Q is required for activity-induced Msp300/Nesprin-1 expression and new synapse formation. The Journal of cell biology 20 32040548
2020 SYNCRIP, a new player in pri-let-7a processing. RNA (New York, N.Y.) 19 31907208
2020 Neuronal upregulation of Prospero protein is driven by alternative mRNA polyadenylation and Syncrip-mediated mRNA stabilisation. Biology open 19 32205310
2021 Further evidence for de novo variants in SYNCRIP as the cause of a neurodevelopmental disorder. Human mutation 18 34157790
2023 RNA binding protein SYNCRIP maintains proteostasis and self-renewal of hematopoietic stem and progenitor cells. Nature communications 17 37085479
2022 SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence. Acta pharmaceutica Sinica. B 17 35967275
2013 Identification of proteins specifically interacting with YB-1 mRNA 3' UTR and the effect of hnRNP Q on YB-1 mRNA translation. Biochemistry. Biokhimiia 17 23980891
2016 HnRNP Q Has a Suppressive Role in the Translation of Mouse Cryptochrome1. PloS one 15 27392095
2019 hnRNP Q Regulates Internal Ribosome Entry Site-Mediated fmr1 Translation in Neurons. Molecular and cellular biology 13 30478144
2017 The hnRNP Q-like gene is retroinserted into the B chromosomes of the cichlid fish Astatotilapia latifasciata. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 13 28776210
2006 The acidic domain of hnRNPQ (NSAP1) has structural similarity to Barstar and binds to Apobec1. Biochemical and biophysical research communications 13 17010310
2022 SYNCRIP Modulates the Epithelial-Mesenchymal Transition in Hepatocytes and HCC Cells. International journal of molecular sciences 11 35055098
2020 The cytoplasmic SYNCRIP mRNA interactome of mammalian neurons. RNA biology 11 33030396
2021 SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation. Veterinary research 10 34034820
2016 The acidic domain is a unique structural feature of the splicing factor SYNCRIP. Protein science : a publication of the Protein Society 9 27081926
2021 RNA-binding protein syncrip regulates starvation-induced hyperactivity in adult Drosophila. PLoS genetics 7 33617535
2016 Synaptotagmin 7 and SYNCRIP proteins are ubiquitously expressed in the rat brain and co-localize in Purkinje neurons. Journal of chemical neuroanatomy 7 27771350
2024 RNA-binding protein SYNCRIP contributes to neuropathic pain through stabilising CCR2 expression in primary sensory neurones. British journal of anaesthesia 6 39244479
2019 HNRNP Q suppresses polyglutamine huntingtin aggregation by post-transcriptional regulation of vaccinia-related kinase 2. Journal of neurochemistry 6 30488434
2019 CRISPR/Cas-mediated Fubp1 silencing disrupts circadian oscillation of Per1 protein via downregulating Syncrip expression. Cell biology international 5 31535751
2025 Posttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by Syncrip. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 4 39776340
2025 Imp/IGF2BP and Syp/SYNCRIP temporal RNA interactomes uncover combinatorial networks of regulators of Drosophila brain development. Science advances 4 39919181
2019 The RNA-binding protein hnRNP Q represses translation of the clock gene Bmal1 in murine cells. The Journal of biological chemistry 4 30948510
2025 Negative regulation of miRNA sorting into EVs is mediated by the capacity of RBP PCBP2 to impair the SYNCRIP-dependent miRNA loading. eLife 3 40601477
2024 hnRNP Q/SYNCRIP interacts with LIN28B and modulates the LIN28B/let-7 axis in human hepatoma cells. PloS one 3 38976670
2021 hnRNP Q and hnRNP A1 Regulate the Translation of Cofilin in Response to Transient Oxygen-Glucose Deprivation in Hippocampal Neurons. Cells 3 34944075
2024 The up-regulation of SYNCRIP promotes the proliferation and tumorigenesis via DNMT3A/p16 in colorectal cancer. Scientific reports 2 39284825
2026 Circular RNA circNrip1 Interacts with SYNCRIP to Promote Neuropathic Pain by Stabilizing Tlr2 mRNA in Primary Sensory Neurons. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41957537
2026 Time-resolved proteomics reveals five modules of stress granule disassembly and identifies SYNCRIP as a late-phase clearance factor. The international journal of biochemistry & cell biology 0 42061552

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