| 1994 |
hnRNP A1 is a sequence-specific RNA-binding protein; its consensus high-affinity binding site is UAGGGA/U, determined by SELEX from random RNA pools. Both RNA-binding domains (RBDs) act as a single composite to confer specificity, and the highest-affinity winner sequence (containing a duplication separated by two nucleotides) binds with Kd ~1 nM. Oligonucleotides containing this site are potent inhibitors of in vitro pre-mRNA splicing. |
SELEX/selection-amplification from random RNA pools; UV crosslinking; in vitro splicing inhibition assay |
The EMBO journal |
High |
7510636
|
| 1994 |
hnRNP A1 antagonizes SR proteins (SF2/ASF, SC35) to activate distal 5' splice sites. Two conserved Phe residues in the RNP-1 submotif of each RBD are essential for modulating alternative splicing (but not general pre-mRNA binding). The C-terminal Gly-rich domain is necessary for alternative splicing activity, stable RNA binding, and RNA annealing activity. |
Mutagenesis of recombinant hnRNP A1; in vitro splicing assays; RNA-binding assays |
The EMBO journal |
High |
7957114
|
| 1995 |
A ~40 amino acid segment near the C-terminus of hnRNP A1, designated M9, is necessary and sufficient for nuclear localization. Fusion of M9 to cytoplasmic proteins (β-galactosidase, pyruvate kinase) redirected them to the nucleus. M9 is a novel NLS type distinct from classical basic-type NLS; the RBDs and RGG box are not required for nuclear localization. |
Domain deletion/fusion constructs; subcellular localization by microscopy in cultured cells |
The Journal of cell biology |
High |
7730395
|
| 1996 |
hnRNP A1 selectively interacts with itself and other hnRNP core proteins (and some SR proteins) through its C-terminal Gly-rich domain. This domain is necessary and sufficient for both in vitro binding and in vivo interaction as tested by yeast two-hybrid assay; a novel hydrophobic-repeat protein-binding motif within the Gly-rich domain mediates these interactions. |
In vitro pulldown; yeast two-hybrid assay |
Journal of molecular biology |
Medium |
8676373
|
| 1998 |
hnRNP A1 participates in telomere biogenesis in mammals. A1-deficient mouse cells have shorter telomeres; restoring A1 expression increases telomere length. UP1 (N-terminal fragment of A1) binds single-stranded vertebrate telomeric repeats directly and specifically in vitro, and can recover telomerase activity from cell lysate, implying A1/UP1 modulates telomere length via interaction with telomerase. |
A1-deficient mouse cell line analysis; telomere length assay; in vitro DNA binding; telomerase recovery from lysate |
Nature genetics |
High |
9620782
|
| 2001 |
hnRNP A1 inhibits HIV-1 tat intron splicing via a novel intronic splicing silencer (ISS) that overlaps with alternative branch point sequences, blocking U2 snRNP association (but at a step after U2AF binding). Recombinant hnRNP A1 added to depleted nuclear extracts restores splicing inhibition; hnRNP A1 interacts specifically with the ISS sequence. |
hnRNP A1 depletion/reconstitution of nuclear extracts; in vitro splicing assays; RNA-protein binding assays |
The EMBO journal |
High |
11598017
|
| 2001 |
Nuclear accumulation of hnRNP A1 is transcription-dependent: in transcriptionally inactive embryos it equilibrates passively between nucleus and cytoplasm, but in transcriptionally active embryos it concentrates in the nucleus via carrier-mediated (transportin-dependent) import. The presence of nascent transcripts in the nucleus (not cytoplasmic RNA) is the critical event driving nuclear concentration. |
Live imaging and microinjection in mouse embryos; transcription inhibition; nuclear transplantation; wheat germ agglutinin nuclear pore blockade |
Journal of cell science |
High |
11282028
|
| 2002 |
The nucleocytoplasmic shuttling activity of hnRNP A1 is required for normal myelopoiesis and BCR/ABL leukemogenesis. BCR/ABL stabilizes hnRNP A1 by preventing its ubiquitin/proteasome-dependent degradation. A nuclear-export-defective mutant suppresses granulocytic differentiation, enhances apoptosis, and reduces BCR/ABL-dependent colony formation, with downstream loss of C/EBPα and Bcl-XL mRNAs. |
Expression of export-defective mutant in cell lines and primary cells; colony formation; differentiation assays; BCR/ABL transformation model |
Molecular and cellular biology |
Medium |
11884611
|
| 2003 |
hnRNP A1 and hnRNP A/B interact with PABPN1, and co-localize with mutant PABPN1 in intranuclear aggregates in OPMD; hnRNP A1 is sequestered in OPMD patient muscle inclusions, supporting the idea that inclusions act as 'poly(A) RNA traps' interfering with RNA export. |
Yeast two-hybrid screen; GST pulldown; co-immunoprecipitation; co-localization in cellular OPMD model and patient tissue |
The Canadian journal of neurological sciences |
Medium |
12945950
|
| 2003 |
hnRNP A1 binds a downstream intronic silencer (rasISS1) and inhibits c-H-ras IDX exon splicing. Depletion and add-back experiments in nuclear extracts confirm the inhibitory role; SR proteins SC35 and SRp40 counteract this inhibition. |
Depletion/add-back in nuclear extracts; in vitro splicing assays; RNA-protein binding |
Molecular and cellular biology |
High |
12665590
|
| 2003 |
hnRNP A1 binds the 5' half of c-src exon N1 (identified by UV crosslinking and immunoprecipitation) and represses N1 splicing in vitro via a mechanism distinct from PTB-mediated repression and independent of PTB binding sites upstream of N1. |
Site-specific UV crosslinking/immunoprecipitation; addition of purified protein to in vitro splicing reactions |
Molecular and cellular biology |
Medium |
12612063
|
| 2004 |
Transportins 1 (Trn1) and 2b (Trn2b) — but not Trn2a — preferentially bind hnRNP A1 via its M9 shuttling domain, and all three transportins function as import factors for hnRNP A1 in vitro. In digitonin-permeabilized HeLa cells, M9 peptides compete for import of recombinant hnRNP A1. |
In vitro binding assays with RanQ69LGTP; digitonin-permeabilized cell import assays; peptide competition |
RNA |
Medium |
15037768
|
| 2004 |
hnRNP A1 has antagonistic functions relative to SR proteins ASF/SF2 and SC35 in regulating beta-tropomyosin exon 6B splicing; hnRNP A1 represses exon 6B splicing by binding a G-rich intronic sequence. ASF/SF2 and SC35 can displace hnRNP A1 binding at overlapping sites. |
RNA affinity chromatography; hnRNP A1-depleted nuclear extract/add-back; artificial tethering (MS2 fusion); UV crosslinking |
The Journal of biological chemistry |
High |
15208309
|
| 2006 |
hnRNP A1 associates with human telomeres in vivo (ChIP) and stimulates telomerase activity. hnRNP A1 binds both single-stranded and structured (G-quadruplex) telomeric repeats, disrupts G-quadruplex higher-order structure, and its depletion from 293 cell extracts dramatically reduces telomerase activity, which is restored by addition of purified recombinant hnRNP A1. |
In vitro telomerase assay; hnRNP A/B depletion/reconstitution; ChIP; G-quadruplex disruption assay |
RNA |
High |
16603717
|
| 2007 |
hnRNP A1 is required for processing of miR-18a: it binds specifically to the primary RNA pri-miR-18a before Drosha cleavage; depletion of hnRNP A1 reduces in vitro processing of pri-miR-18a and endogenous pre-miR-18a levels; hnRNP A1 is required for miR-18a-mediated repression of a target reporter in vivo. |
In vivo CLIP; in vitro Drosha processing assay; siRNA depletion; reporter assay |
Nature structural & molecular biology |
High |
17558416
|
| 2007 |
hnRNP A1 specifically represses SMN2 exon 7 splicing via binding to an exonic splicing silencer (ESS); hnRNP A1 depletion specifically restores SMN2 exon 7 inclusion. Strong and specific interaction between hnRNPA1 and SMN2 exon 7 was demonstrated by two independent methods. |
siRNA depletion; RNA-protein interaction assays (two methods); in vivo and in vitro splicing |
Human molecular genetics |
High |
17884807
|
| 2007 |
hnRNP A1 facilitates HCV replication by interacting with NS5b (RNA-dependent RNA polymerase) and binding both the 5' NTR and 3' NTR of HCV RNA; knockdown of hnRNP A1 or expression of C-terminally truncated hnRNP A1 reduces HCV replication. |
Co-immunoprecipitation; yeast two-hybrid; RNA-protein binding; siRNA knockdown; truncation mutant overexpression |
Journal of virology |
Medium |
17229681
|
| 2009 |
hnRNP A1 binds cooperatively to RNA, initiating at a high-affinity ESS and spreading in a 3'-to-5' direction (with some 5'-to-3' spreading also possible). Cooperative spreading displaces SR protein binding to an exonic splicing enhancer and can unwind RNA hairpins upon binding. Two distant high-affinity sites on the same RNA facilitate inter-site spreading. |
In vitro RNA binding and splicing assays with purified hnRNP A1; gel-shift; in vitro helicase/unwinding assays |
Molecular and cellular biology |
High |
19667073
|
| 2009 |
hnRNP A1 and hnRNP H can collaborate to modulate 5' splice site selection through homotypic and heterotypic protein-protein interactions (documented by BRET in live cells) via their glycine-rich domains; the GRD of hnRNP A1 can functionally replace that of hnRNP H. |
In vitro splicing assays; BRET in live cells; domain swap experiments |
RNA |
Medium |
19926721
|
| 2010 |
hnRNP A1 acts as a negative regulator of let-7a biogenesis by binding the conserved terminal loop of pri-let-7a-1, inhibiting Drosha processing. hnRNP A1 binding interferes with KSRP binding (a positive regulator), creating antagonistic regulation of let-7a levels. |
RNA binding assays; Drosha processing in cell extracts; siRNA depletion; ectopic overexpression; competition binding assay |
Nature structural & molecular biology |
High |
20639884
|
| 2011 |
hnRNP A1 recapitulates a novel RPA-displacing activity that specifically removes RPA (but not POT1) from telomeric ssDNA, facilitating the RPA-to-POT1 switch required for telomere capping after replication. TERRA inhibits this displacing activity in early S phase and promotes POT1 binding by removing hnRNP A1, coordinating the switch. |
In vitro ssDNA-binding competition assay with purified proteins; cell extract fractionation; identification by purified protein reconstitution |
Nature |
High |
21399625
|
| 2012 |
hnRNP A1 proofreads 3' splice site recognition by U2AF: it forms a ternary complex with U2AF heterodimer on AG-containing/uridine-rich RNAs, while displacing U2AF from non-AG-containing sequences. This activity requires the glycine-rich domain of hnRNP A1, and hnRNP A1 is required for U2AF-mediated recruitment of U2 snRNP. |
In vitro depletion/reconstitution; purified component binding assays; NMR; in vivo splicing assays |
Molecular cell |
High |
22325350
|
| 2012 |
VRK1 phosphorylates hnRNP A1, potentiating its binding to telomeric ssDNA and telomerase RNA in vitro and enhancing telomerase activity. VRK1 deficiency in mouse male germ cells induces telomere shortening and activation of DNA-damage signaling. |
In vitro kinase assay; telomere length assay; telomerase activity assay; VRK1 knockout mouse germ cells |
Nucleic acids research |
Medium |
22740652
|
| 2013 |
Mutations in the prion-like domain (PrLD) of hnRNPA1 (e.g., strengthening a steric zipper motif) cause multisystem proteinopathy and ALS. Wild-type hnRNPA1 forms self-seeding fibrils; disease mutations exacerbate fibril formation and promote excess incorporation into stress granules and cytoplasmic inclusions in animal models. |
Fibril formation assay; cross-seeding experiments; stress granule analysis in cells and animal models; mutant protein expression |
Nature |
High |
23455423
|
| 2013 |
hnRNP A1 controls a splicing regulatory circuit promoting mesenchymal-to-epithelial transition (MET) by binding the Ron exon 11 silencer and antagonizing SRSF1-induced exon 11 skipping (ΔRon). hnRNP A1 also affects Ron splicing indirectly by regulating hnRNP A2/B1 expression levels. |
RNA binding/competition assays; splicing assays; siRNA knockdown; ectopic expression; cell migration assays |
Nucleic acids research |
Medium |
23863836
|
| 2013 |
hnRNP A1 regulates HMGCR alternative splicing by directly binding to the rs3846662 SNP region to promote exon 13 skipping; overexpression of hnRNPA1 increases the HMGCR13(-)/total HMGCR ratio, stabilizes the HMGCR13(-) transcript specifically, and reduces HMGCR enzyme activity, while enhancing LDL-C uptake. |
RNA-protein binding assays (EMSA); overexpression in human cell lines; RT-PCR splicing assay; enzyme activity assay; LDL uptake assay |
Human molecular genetics |
Medium |
24001602
|
| 2014 |
S6K2 phosphorylates hnRNPA1 on novel Ser4/6 sites (N-terminal), increasing its association with BCL-XL and XIAP mRNAs to promote their nuclear export. In the cytoplasm, phospho-S4/6-hnRNPA1 dissociates from these mRNAs, de-repressing their IRES-mediated translation. This is followed by phosphorylation-dependent association with 14-3-3, leading to hnRNPA1 sumoylation on K183 and nuclear re-import. |
In vitro kinase assay; phospho-mutant expression (S4/6A); RIP; nuclear/cytoplasmic fractionation; IRES-reporter assays; Co-IP |
Nucleic acids research |
High |
25324306
|
| 2015 |
DNA-PKcs phosphorylates hnRNP-A1 during G2/M phase; this phosphorylation promotes the RPA-to-POT1 switch on telomeric single-stranded 3' overhangs. Loss of hnRNP-A1 or DNA-PKcs-dependent hnRNP-A1 phosphorylation impairs this switch, causing DNA damage response at telomeres during mitosis and induction of fragile telomeres. |
In vitro kinase assay; cell cycle analysis; telomere FISH; chromatin fractionation; RPA/POT1 binding assays at telomeres |
Nucleic acids research |
Medium |
25999341
|
| 2015 |
ALS mutations in ubiquilin-2 reduce its interaction with hnRNPA1 (glycine-rich domain); the hnRNPA1 D262V ALS mutation fails to bind wild-type ubiquilin-2. Ubiquilin-2 functions to stabilize hnRNPA1 (knockdown increases hnRNPA1 turnover), and ALS mutations in UBQLN2 correlate with increased hnRNPA1 cytoplasmic translocation. |
Yeast two-hybrid; in vitro binding; co-immunoprecipitation; pulse-chase/protein stability assay; subcellular fractionation |
Human molecular genetics |
Medium |
25616961
|
| 2015 |
hnRNPA1 expression is regulated by a NF-κB2/p52:c-Myc transcriptional circuit, and hnRNPA1 promotes alternative splicing of androgen receptor to generate AR-V7 splice variants in prostate cancer. Knockdown of hnRNPA1 reduces AR-V7 and resensitizes enzalutamide-resistant cells to treatment. |
ChIP; siRNA knockdown; RT-PCR splicing assay; reporter assay; cell viability |
Molecular cancer therapeutics |
Medium |
26056150
|
| 2016 |
TRAF6 directly ubiquitinates hnRNPA1 (identified by global ubiquitin screen); this ubiquitination regulates alternative splicing of Arhgap1, which activates Cdc42 GTPase and causes hematopoietic defects in TRAF6-overexpressing HSPCs. |
Global ubiquitin screen (mass spectrometry); co-immunoprecipitation; in vitro ubiquitination assay; splicing analysis; Cdc42 activity assay |
Nature immunology |
High |
28024152
|
| 2016 |
SPSB1 (an E3 ubiquitin ligase adaptor) conjugates K29-linked polyubiquitin chains onto hnRNP A1 in response to EGF signaling. EGF-induced ubiquitylation of hnRNP A1 together with SRPK activation upregulates the Rac1b splicing isoform to promote cell motility. |
Co-IP; ubiquitin chain type analysis; EGF treatment; siRNA knockdown; alternative splicing assay; cell migration assay |
Cell research |
Medium |
28084329
|
| 2017 |
PRMT5 methylates hnRNP A1 on R218 and R225 (symmetric dimethylation); this methylation facilitates hnRNP A1 interaction with IRES RNA to promote IRES-dependent translation of Cyclin D1 and c-Myc. |
In vitro methylation assay; mass spectrometry; IRES-reporter assays; RNA-protein binding (pulldown); mutant hnRNP A1 |
Nucleic acids research |
High |
28115626
|
| 2017 |
The two tandem RRM domains of hnRNP A1 bind simultaneously to a single bipartite ISS-N1 motif (controlling SMN exon 7 splicing): RRM2 binds the upstream motif and RRM1 binds the downstream motif. Disruption of inter-RRM interaction or loss of RNA binding by either RRM impairs splicing repression. Both ISS-N1 binding sites contribute cumulatively to repression. |
Solution NMR structures of RRM-RNA complexes; in-cell splicing assays; mutagenesis |
eLife |
High |
28650318
|
| 2017 |
HNRNPA1 globally occupies intronic regions near 5' splice sites in vivo (iCLIP), with binding in proximal introns associated with exon repression. The hnRNP A1 consensus binding motif was defined in vivo, enabling identification of therapeutic SSO targets. |
iCLIP (individual-nucleotide resolution CLIP); minigene splicing assays; SSO-mediated exon rescue |
BMC biology |
Medium |
27380775
|
| 2017 |
hnRNP A1 directly binds the 5' UTR G-quadruplex of RON/MTS1R mRNA and activates its IRES-mediated translation; cytoplasmic hnRNP A1 promotes RON translation and cell migration in vitro. |
RNA pulldown; reporter (IRES-luciferase); cell migration assay; cytoplasmic hnRNP A1 mutant expression |
Oncotarget |
Medium |
26930004
|
| 2018 |
β-hydroxybutyrate (β-HB) directly binds hnRNP A1; this binding enhances hnRNP A1 interaction with Oct4 mRNA, stabilizes Oct4 mRNA and protein expression, and leads to increased Lamin B1 to prevent vascular cell senescence. |
Protein pulldown/mass spectrometry; RIP; Oct4 mRNA stability assay; senescence assays; in vivo mouse experiments |
Molecular cell |
Medium |
30197300
|
| 2018 |
The RGG-box of hnRNPA1 specifically recognizes the loop-containing telomere G-quadruplex DNA (but not single-stranded DNA); loop nucleotide identity is important. The RGG-box enhances the G-quadruplex unfolding activity of the adjacent UP1 domain, acting synergistically for complete telomere G-quadruplex DNA unfolding. |
In vitro binding (EMSA, fluorescence); G-quadruplex unfolding assay; domain deletion/truncation analysis |
Nucleic acids research |
Medium |
30247678
|
| 2018 |
lncSHGL recruits hnRNPA1 to enhance translation efficiency of CALM mRNAs, increasing calmodulin protein levels and activating the CaM/PI3K/Akt pathway independent of insulin. Hepatic overexpression of hnRNPA1 alone activates this pathway and ameliorates hyperglycemia and steatosis in obese mice. |
RNA pulldown; RIP; polysome profiling; in vivo AAV-mediated overexpression in mice; metabolic phenotyping |
Diabetes |
Medium |
29382663
|
| 2018 |
O-GlcNAcylation of hnRNP A1 increases its interaction with Transportin1 (Trn1) and promotes nuclear sequestration, whereas phosphorylation reduces Trn1 interaction and promotes cytoplasmic accumulation. Several novel O-GlcNAcylation and phosphorylation sites in hnRNP A1 were mapped. |
O-GlcNAc site mapping by mass spectrometry; co-immunoprecipitation; subcellular fractionation; OGT inhibitor treatment |
Experimental cell research |
Medium |
27913144
|
| 2018 |
HNRNPA1 promotes recognition of U2AF2 'decoy' splice sites in vivo (including Alu-derived sequences), shifting U2AF2 binding away from bona fide 3' splice sites of alternative cassette exons, thereby regulating exon definition. |
iCLIP of U2AF2 in control vs. HNRNPA1 overexpression cells; splicing analysis |
Genome research |
Medium |
29650551
|
| 2018 |
hnRNPA1 interacts with the G-quadruplex in the KRAS promoter GA-element and stimulates KRAS transcription; the hnRNPA1 interaction with G4 DNA in the promoter facilitates transcription of TRA2B similarly. |
Circular dichroism; EMSA; chromatin immunoprecipitation; promoter-reporter assay; knockdown |
Scientific reports |
Medium |
31311954
|
| 2019 |
SIRT1 and SIRT6 deacetylate hnRNP A1 at four lysine residues under glucose starvation conditions; deacetylated hnRNP A1 reduces PKM2 and increases PKM1 alternative splicing, inhibiting glycolysis and HCC cell proliferation. |
Co-immunoprecipitation; mass spectrometry (acetylation site mapping); PKM splicing assay; glycolysis assays; mutant hnRNP A1 |
Oncogene |
Medium |
30858544
|
| 2019 |
hnRNP A1 directly binds the 3' UTR of SIRT1 mRNA and promotes its stability, increasing SIRT1 expression. This hnRNP A1-SIRT1-NF-κB pathway delays cellular senescence and SASP by deacetylating NF-κB and blunting IL-6/IL-8 transcription. |
RIP; mRNA stability assay; 3' UTR reporter; SIRT1-dependent rescue; senescence assays |
Aging cell |
Medium |
27613566
|
| 2020 |
The cryo-EM structure of hnRNPA1 LC domain amyloid fibrils reveals that the PY-NLS (M9/nuclear localization sequence) forms the fibril core. Residues involved in Kapβ2 (karyopherin-β2) binding also make key interactions to stabilize the fibril; ALS/MSP mutations map to the fibril core. This explains Kapβ2's amyloid disaggregase activity. |
Cryo-electron microscopy (fibril structure determination); mutagenesis; fibril formation assays |
Nature communications |
High |
33311513
|
| 2020 |
Systemic overexpression of HNRNPA1 in a DM1 mouse model (via AAV) shifts DM1-relevant splicing targets to fetal isoforms and causes muscle weakness/myopathy. HITS-CLIP reveals direct interactions of HNRNPA1 with these splicing targets in vivo. HNRNPA1 protein levels decrease during postnatal development but are elevated in DM1 skeletal muscle. |
AAV-mediated overexpression; HITS-CLIP in vivo; splicing analysis; muscle function assays |
PNAS |
High |
32086392
|
| 2020 |
The RGG-box of hnRNPA1 specifically recognizes loop-containing TERRA RNA G-quadruplexes but not single-stranded RNA; the UP1 domain + RGG-box act together to destabilize loop-containing TERRA G-quadruplexes more efficiently than those without loops. |
In vitro binding assays (EMSA, fluorescence); G-quadruplex unfolding assay; domain truncation |
Nucleic acids research |
Medium |
32128583
|
| 2020 |
hnRNP A1 is an IRES trans-activating factor (ITAF) for HIV-1, HTLV-1, and MMTV IRESs. Post-translational modifications of hnRNP A1 differentially modulate retroviral IRES activity: PRMT5-induced symmetric dimethylation enables stimulation of HIV-1 and HTLV-1 IRESs while reducing MMTV IRES stimulation; phospho-S4/6D preferentially stimulates the MMTV IRES. |
IRES-reporter assays; post-translational modification mutants; knockdown/rescue; in vitro methylation |
Nucleic acids research |
Medium |
32960212
|
| 2021 |
PRMT4/5/7-mediated arginine methylation of hnRNPA1 (at multiple sites) regulates hnRNPA1 binding to RNA and several alternative splicing events; co-inhibition of PRMT4/5/7 synergistically suppresses cancer cell growth. |
Mass spectrometry (methylproteome); RNA binding assays; alternative splicing analysis; pharmacological PRMT inhibition |
Nature communications |
Medium |
33782401
|
| 2021 |
hnRNP A1/A2 proteins directly assemble onto 7SK snRNA stem loop 3 (SL3), binding with selectivity via context-dependent mechanisms; up to four hnRNP A1 proteins bind along SL3, preserving its overall structural integrity. SL3 architecture positions minimal hnRNP A1/A2 binding sites (5'-Y/RAG-3') in different local environments modulating assembly. |
DMS probing of RNA structure; ITC (calorimetry); SEC-MALS-SAXS; phylogenetic analysis |
Journal of molecular biology |
Medium |
33684393
|
| 2021 |
HNRNPA1 positively regulates VRK1 translation by binding directly to the 3' UTR of VRK1 mRNA; this increases cyclin D1 expression via VRK1-mediated CREB phosphorylation, promoting lung cancer cell proliferation. |
RNA pulldown; RIP; polysome fractionation; VRK1 translation reporter; CREB phosphorylation assay; knockdown/overexpression |
International journal of molecular sciences |
Medium |
34071140
|
| 2021 |
4 novel and 2 known HNRNPA1 mutations (P288A, D262V, *321Eext*6, *321Qext*6, G304Nfs*3) have different effects on hnRNPA1 fibrillization, liquid-liquid phase separation, and stress granule dynamics: P288A accelerates fibrillization and decelerates SG disassembly; *321Eext*6 has no effect on fibrillization but decelerates SG disassembly; G304Nfs*3 decelerates fibrillization and impairs liquid phase separation. |
In vitro fibrillization assay; LLPS assay; live-cell stress granule dynamics (imaging) |
JCI insight |
Medium |
34291734
|
| 2024 |
Dysfunction of hnRNP A1 in MS neurons causes differential binding to RNA targets and aberrant alternative RNA splicing of neuronal function and RNA homeostasis genes, contributing to neurodegeneration. CLIPseq in EAE models confirms differential binding to aberrantly spliced targets; dysfunctional hnRNP A1 expression in neurons caused neurite loss and identical splicing changes. |
RNAseq (human MS brain); CLIPseq in vivo (EAE model); neuronal expression of dysfunctional hnRNP A1 + neurite morphometry |
Nature communications |
High |
38191621
|
| 2024 |
Adipocyte-specific knockout of Hnrnpa1 in obese mice increases macrophage infiltration and inflammatory gene expression in white adipose tissue, exacerbating insulin resistance and hepatic steatosis. Mechanistically, HNRNPA1 interacts with Ccl2 mRNA and regulates its stability. |
Adipocyte-specific Hnrnpa1 knockout mouse; metabolic phenotyping; RNA pulldown/RIP for Ccl2 mRNA; mRNA stability assay |
Diabetes |
Medium |
38320300
|
| 2015 |
hnRNP A1 reduction (by RNAi or cytoplasmic retention) increases RNA Pol II transcription of a reporter gene and increases CDK9 association with the repressor 7SK RNA, compromising promoter-distal transcription recovery after pause release; transcriptome analysis shows >50% of genes affected by A1/A2 depletion overlap with those affected by CDK9 inhibition. |
siRNA knockdown; transcriptome analysis; ChIP of RNA Pol II and CDK9; DRB treatment; reporter assay |
PloS one |
Medium |
26011126
|