Affinage

PABPN1

Polyadenylate-binding protein 2 · UniProt Q86U42

Length
306 aa
Mass
32.7 kDa
Annotated
2026-04-29
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PABPN1 is a nuclear poly(A)-binding protein that controls poly(A) tail length, couples polyadenylation to downstream RNA processing events, and undergoes liquid-liquid phase separation to organize nuclear RNA domains. It stimulates poly(A) polymerase and forms oligomeric particles on nascent poly(A) tails whose defined size sets the ~250 nt tail length; it associates cotranscriptionally with RNA polymerase II, accompanies mRNPs to the nuclear pore, suppresses usage of proximal polyadenylation sites, and promotes splicing of terminal introns by recruiting RBM26/RBM27 (PMID:10731412, PMID:12749861, PMID:37661812, PMID:25896913). PABPN1 autoregulates its own expression through intron retention coupled to nuclear exosome (Rrp6)-dependent decay, forms nuclear poly(A) domains via phase separation in oocytes to stabilize growth-phase transcripts, and in the cytoplasm facilitates maternal mRNA clearance by docking on uridylated transcripts and recruiting the exoribonuclease DIS3L2 (PMID:25963658, PMID:36306357, PMID:34904664). Short GCG-repeat expansions encoding 12–17 alanines cause oculopharyngeal muscular dystrophy (OPMD); the expanded polyalanine tract adopts an α-helical conformation that promotes amyloid-like fibril formation and intranuclear inclusions that sequester hnRNPs, PRMTs, and Hsp70, with pathology depending on the RNA-binding activity of PABPN1 rather than polyalanine toxicity alone (PMID:9462747, PMID:14627730, PMID:16642034, PMID:19641605).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    The genetic cause of OPMD was unknown; identification of short GCG expansions in PABPN1 established that polyalanine expansion from 10 to 12–17 residues is the causative mutation and linked the protein to intranuclear filament inclusions in skeletal muscle.

    Evidence Linkage analysis and mutation screening in 144 OPMD families

    PMID:9462747

    Open questions at the time
    • Mechanism by which expanded polyalanine causes inclusions was unknown
    • Why pathology is muscle-specific was not addressed
    • Whether inclusions are causative or correlative was unresolved
  2. 2000 High

    How PABPN1 sets poly(A) tail length was unclear; EM/SFM revealed that PABPN1 forms discrete oligomeric particles on poly(A) whose maximum size corresponds to the ~250 nt in vivo tail length, providing a molecular ruler model for polyadenylation control.

    Evidence Electron microscopy, scanning force microscopy, gel shift, and filter binding of PABP2·poly(A) complexes

    PMID:10731412

    Open questions at the time
    • How the particle signals termination of polyadenylation was not defined
    • In vivo validation of the ruler model was lacking
  3. 2000 High

    The subnuclear localization of PABPN1 was uncharacterized; speckle targeting was shown to depend strictly on poly(A) RNA binding rather than a dedicated localization signal, and expanded PABPN1 was sufficient to drive intranuclear aggregate formation in cell models.

    Evidence Transcription/poly(A) synthesis inhibition, RNA-binding mutants, immunofluorescence in HeLa cells; expression of expanded vs. normal PABPN1 in COS-7 cells

    PMID:10825302 PMID:11079546

    Open questions at the time
    • Whether speckle localization is functionally required for PABPN1 activity was unknown
    • Role of post-translational modifications in localization was not tested
  4. 2001 High

    Whether PABPN1 oligomerization was required for aggregate-mediated toxicity was untested; deletion of either of two oligomerization domains prevented both nuclear aggregation and cell death, establishing self-oligomerization as essential for OPMD-associated inclusion pathology.

    Evidence Deletion mutagenesis of oligomerization domains in mutant PABPN1; COS-7 expression and cell death assays

    PMID:11689481

    Open questions at the time
    • Structural basis of oligomerization domain function was unresolved
    • Whether oligomerization is also required for normal poly(A) tail length control was unknown
  5. 2003 High

    Whether expanded PABPN1 forms canonical amyloid structures and what proteins are sequestered was unknown; biophysical studies showed antiparallel β-sheet amyloid-like fibrils from the expanded N-terminus, and expanded PABPN1 was shown to sequester hnRNP A1/A/B in inclusions in patient muscle.

    Evidence ThT fluorescence, CD spectroscopy, EM of recombinant expanded PABPN1; yeast two-hybrid, GST pull-down, co-IP, and immunofluorescence in patient tissue for hnRNP interactions

    PMID:12945950 PMID:14627730

    Open questions at the time
    • Whether sequestration of hnRNPs functionally contributes to disease was not demonstrated
    • Full inventory of sequestered factors was incomplete
  6. 2003 High

    Where PABPN1 acts along the gene expression pathway was unclear; cryo-immunoEM showed it associates with RNA Pol II on chromatin, accompanies mRNPs to the nuclear pore, and is stripped during or after translocation, defining its life cycle on the transcript.

    Evidence Cryo-immunoelectron microscopy of Chironomus tentans Balbiani ring mRNPs at sequential stages

    PMID:12749861

    Open questions at the time
    • Mechanism of PABPN1 stripping at the pore was unknown
    • Whether this cotranscriptional recruitment mechanism is conserved in mammals was not directly shown
  7. 2005 High

    PABPN1 was considered exclusively a nuclear polyadenylation factor; Drosophila genetics revealed an unexpected cytoplasmic role in shortening poly(A) tails of specific maternal mRNAs (oskar, cyclin B) together with CCR4, controlling protein levels and embryonic development.

    Evidence Genetic loss-of-function in Drosophila; poly(A) tail assays; genetic interaction with CCR4

    PMID:16198293

    Open questions at the time
    • Whether this cytoplasmic deadenylation role is conserved in mammals was unknown at this time
    • Direct physical interaction with CCR4 was not shown
  8. 2006 High

    Whether OPMD pathology is driven by polyalanine toxicity or by PABPN1's RNA-processing function was debated; Drosophila studies showed that muscle degeneration requires the RNA-binding domain but not the polyalanine tract, establishing that disease stems from dysregulated RNA processing.

    Evidence Transgenic Drosophila with PABPN1 domain-specific mutants; muscle degeneration and inclusion phenotyping

    PMID:16642034

    Open questions at the time
    • Specific RNA targets whose misprocessing drives muscle degeneration were not identified
    • Whether the same principle applies in mammalian OPMD models was not confirmed
  9. 2009 Medium

    The structural basis for preferential interaction of expanded PABPN1 with chaperones was unknown; pull-down assays and MD simulations revealed that polyalanine expansion converts the disordered N-terminus to a stable helix, enhancing binding to Hsp70, PRMT1, and PRMT3, which are then sequestered in inclusions.

    Evidence Pull-down of expanded vs. WT PABPN1; immunofluorescence in OPMD patient muscle; molecular dynamics simulations

    PMID:19641605

    Open questions at the time
    • Whether sequestration of PRMTs has functional consequences for arginine methylation in muscle was not tested
    • Structural model was based on simulation without experimental structure validation
  10. 2013 High

    How PABPN1 levels are maintained was unknown; a novel autoregulatory circuit was identified in which PABPN1 promotes retention of its own 3'-terminal intron by binding an A-rich element in the 3' UTR, targeting the unspliced pre-mRNA for Rrp6-dependent nuclear exosome decay.

    Evidence RT-PCR intron retention assays; PABPN1 and Rrp6 knockdown in human cells; RNA immunoprecipitation

    PMID:25963658

    Open questions at the time
    • Whether this autoregulatory mechanism is disrupted in OPMD was not examined
    • Quantitative contribution of this pathway vs. other regulatory circuits (HuR, circPABPN1) was not determined
  11. 2015 High

    Whether PABPN1 plays a direct role in splicing was uncertain; depletion experiments revealed that PABPN1 promotes splicing of a subset of post-transcriptionally excised terminal introns, requiring its RNA-binding and PAP-stimulatory activities, linking poly(A) tail addition to splicing commitment.

    Evidence PABPN1 RNAi in human cells; splicing assays; ChIP for splicing factor recruitment; domain mutant complementation

    PMID:25896913

    Open questions at the time
    • Identity of recruited splicing factors was not fully resolved at this stage
    • Whether intron retention phenotypes in OPMD are direct consequences of this function was not tested
  12. 2017 High

    PABPN1's interaction partners in muscle and feedback regulation of its own translation were poorly defined; MATR3 was identified as a co-regulator of APA and intron retention in skeletal muscle, while circPABPN1 was shown to compete with PABPN1 mRNA for HuR binding, suppressing PABPN1 translation.

    Evidence Co-IP/MS from mouse muscle (MATR3); HuR-RIP with circRNA sequencing; polysome profiling and competition assays

    PMID:28080204 PMID:28977530

    Open questions at the time
    • Whether MATR3-PABPN1 interaction is disrupted in OPMD was not fully resolved
    • Stoichiometric relationship between circPABPN1 and PABPN1 mRNA in different tissues was unknown
  13. 2022 High

    PABPN1's roles in oocyte biology and early embryonic development were unknown; conditional knockout revealed that PABPN1 drives NPAD formation through LLPS to stabilize oocyte transcripts (causing sterility when lost), and separately mediates cytoplasmic maternal mRNA clearance by recognizing uridylated tails and recruiting DIS3L2.

    Evidence Pabpn1 cKO in mouse oocytes with LLPS domain analysis and transcript stability assays; Pabpn1 KO embryos with RIP, uridylation assays, and DIS3L2 co-IP

    PMID:34904664 PMID:36306357

    Open questions at the time
    • Whether NPAD formation occurs in somatic cells was not determined
    • How PABPN1 switches from nuclear poly(A)-binding to cytoplasmic uridylated-RNA recognition was mechanistically unresolved
  14. 2023 High

    The mechanism by which PABPN1 promotes terminal intron splicing was incomplete; TurboID proximity labeling and tethering experiments identified RBM26/RBM27 as direct PABPN1-recruited effectors that couple poly(A) tail presence to spliceosome engagement at last introns with weak 3' splice sites.

    Evidence PABPN1 knockdown + RNA-seq in HeLa; tethering to non-polyadenylated transcripts; TurboID-MS interactome; co-IP of RBM27 with domain mapping

    PMID:37661812

    Open questions at the time
    • Whether RBM26/27 directly contacts spliceosomal components was not shown
    • Contribution of this pathway to OPMD intron retention phenotypes was not tested
  15. 2024 Medium

    How PABPN1 phase separation is regulated by interacting proteins was unknown; SNRPD2 was found to bind the EP domain, disrupt PABPN1 LLPS, and shift polyadenylation toward proximal sites, shortening 3' UTRs and promoting cancer cell proliferation.

    Evidence Co-IP of SNRPD2-PABPN1; LLPS assays with domain mutants; APA profiling; cancer cell functional assays

    PMID:38811444

    Open questions at the time
    • Whether SNRPD2-mediated LLPS disruption occurs in normal tissues was not assessed
    • Structural basis for EP domain interaction with SNRPD2 is lacking
    • In vivo relevance in tumor models was not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the structural basis of PABPN1 oligomeric particle assembly and how particle size signals polyadenylation termination; how PABPN1 switches between nuclear poly(A)-binding and cytoplasmic uridylated-RNA recognition; why OPMD pathology is restricted to specific muscles despite ubiquitous PABPN1 expression; and what the full complement of transcripts affected by PABPN1-dependent APA and terminal intron retention is in disease-relevant tissues.
  • No high-resolution structure of PABPN1 oligomeric particle exists
  • Muscle-specific vulnerability in OPMD remains mechanistically unexplained
  • Genome-wide APA and splicing target maps in OPMD patient muscle are incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 8 GO:0098772 molecular function regulator activity 5 GO:0044183 protein folding chaperone 2
Localization
GO:0005634 nucleus 6 GO:0005654 nucleoplasm 3 GO:0005694 chromosome 2 GO:0005829 cytosol 2
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 1
Partners
ARIH2DIS3L2HNRNPA1MATR3PRMT1RBM26RBM27SNRPD2

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Short GCG expansions in the PABPN1 gene expand the N-terminal polyalanine tract from 10 to 12–17 alanines, causing oculopharyngeal muscular dystrophy (OPMD) and leading to accumulation of nuclear filament inclusions in skeletal muscle fibres. Genetic linkage and mutation analysis in 144 OPMD families Nature genetics High 9462747
2000 PABPN1 (PABP2) bound to poly(A) RNA forms both linear filaments and discrete-sized, compact oligomeric particles (~21 nm diameter) whose maximum size corresponds to poly(A) tails of 200–300 nt, consistent with in vivo poly(A) tail length; filament-to-particle equilibrium is sensitive to ionic strength. Electron microscopy and scanning force microscopy of PABP2·poly(A) complexes; gel mobility shift and nitrocellulose filter binding assays Journal of molecular biology High 10731412
2000 PABPN1 localizes to nuclear speckles strictly as a consequence of its binding to poly(A) RNA; this localization is independent of nuclear import per se but requires functional poly(A) binding (mutants with reduced poly(A) affinity fail to localize to speckles). Inhibition of transcription/poly(A) synthesis at end of mitosis; PABPN1 mutant expression in HeLa cells; immunofluorescence Journal of cell science High 10825302
2000 Expanded PABPN1 (mutant PABP2) protein accumulates exclusively in intranuclear aggregates in muscle fibers of OPMD patients, not in normal controls, suggesting molecular modification (e.g., arginine dimethylation at residues 271–291 may differ in mutant protein). Immunofluorescence with peptide antiserum recognizing residues 271–291 on patient muscle biopsies Muscle & nerve Medium 11003790
2000 Expression of mutated PABP2 (expanded polyalanine) cDNA in COS-7 cells is sufficient to induce its accumulation as intranuclear inclusions, demonstrating that the polyalanine expansion directly drives nuclear aggregate formation. Transfection of normal vs. expanded PABP2 constructs in COS-7 cells; immunofluorescence Annals of neurology High 11079546
2001 PABPN1 oligomerization is mediated by two oligomerization domains (ODs); inactivating either OD by 6–8 amino acid deletions prevents mutant PABPN1-induced nuclear protein aggregation and significantly reduces associated cell death in COS-7 cells. Deletion mutagenesis of ODs in mutant PABPN1; expression in COS-7 cells; immunofluorescence; cell death assay Human molecular genetics High 11689481
2003 PABPN1 interacts with hnRNP A1 and hnRNP A/B; when co-expressed with expanded PABPN1 in COS-7 cells, these proteins co-localize with mutant PABPN1 in insoluble intranuclear aggregates, and hnRNP A1 is sequestered in OPMD nuclear inclusions in patient muscle. Yeast two-hybrid screen; GST pull-down; co-immunoprecipitation; co-localization in OPMD patient muscle and cellular model The Canadian journal of neurological sciences High 12945950
2003 Polyalanine-expanded PABPN1 N-terminal fragments form amyloid-like fibrils with antiparallel beta-sheet structure; expansion of poly-L-alanine to maximal OPMD length increases alpha-helical content and fibril formation that can be seeded. Recombinant protein production; ThT fluorescence; CD spectroscopy; electron microscopy; seeding experiments Protein science High 14627730
2003 PABPN1 is associated with RNA polymerase II along the chromatin axis and accompanies the released mRNA ribonucleoprotein (mRNP) to the nuclear pore, but is largely absent on the cytoplasmic side, indicating PABPN1 is displaced during or shortly after nuclear pore translocation. Cryo-immunoelectron microscopy of Chironomus tentans salivary gland Balbiani ring mRNPs at various stages of assembly and transport Experimental cell research High 12749861
2005 In Drosophila, PABP2 is required for poly(A) tail synthesis and stimulation of poly(A) polymerase in the nucleus, but also unexpectedly acts in the cytoplasm to shorten poly(A) tails of specific maternal mRNAs (oskar, cyclin B) together with the deadenylase CCR4, thereby controlling Cyclin B protein levels and embryonic development. Genetic loss-of-function analysis in Drosophila; poly(A) tail length assays; western blotting; genetic interaction with CCR4 Developmental cell High 16198293
2005 Normal PABPN1 is inherently aggregation-prone in HeLa and myogenic C2 cells; inclusion formation depends on domains required for stimulation of poly(A) polymerase, not exclusively on the polyalanine tract. FRAP experiments show that both normal and expanded PABPN1 molecules exchange rapidly in and out of inclusions, arguing they are not irreversibly sequestered. Exogenous expression of PABPN1 variants in HeLa and C2 cells; FRAP live imaging; inclusion formation assay RNA (New York, N.Y.) High 15811916
2005 Fission yeast Pab2 (ortholog of PABPN1) is cotranscriptionally recruited to active genes via nascent mRNPs, preceding arrival of typical 3'-processing factors, and also associates with translating polysomes after nuclear export. Chromatin immunoprecipitation (ChIP) with RNase controls; tandem affinity purification–mass spectrometry; polysome fractionation Nucleic acids research High 19336419
2006 In a Drosophila OPMD model, muscle degeneration requires the RNA-binding domain of PABPN1 and its function in RNA binding, not the polyalanine tract per se, demonstrating that OPMD pathology stems from an intrinsic property of PABPN1 activity, not polyalanine toxicity alone. Transgenic Drosophila expressing PABPN1 variants (polyalanine deletion, RNA-binding domain mutation); muscle degeneration phenotyping; nuclear inclusion quantification The EMBO journal High 16642034
2008 Wild-type PABPN1 exerts an anti-apoptotic function by promoting translation of XIAP (X-linked inhibitor of apoptosis protein); PABPN1 knockdown sensitizes cells to apoptosis and mutant PABPN1 partially loses this activity. PABPN1 overexpression/knockdown in cells and mouse models; staurosporine and Bax-induced apoptosis assays; XIAP protein level measurement by western blot Human molecular genetics Medium 18178579
2008 Deletion of the polyalanine tract in PABPN1 induces aggregates that span both sides of the nuclear membrane, indicating a role for the N-terminal polyalanine tract in nucleocytoplasmic transport of PABPN1. Expression of polyalanine-deletion PABPN1 constructs in cells; confocal immunofluorescence Experimental cell research Medium 18367172
2009 Expanded PABPN1 preferentially binds heat shock proteins (Hsp70) and type I arginine methyltransferases (PRMT1 and PRMT3) compared to wild-type PABPN1; molecular simulations suggest expansion converts a disordered N-terminal region to a stable helix, promoting this preferential interaction and their sequestration in intranuclear inclusions. Pull-down assays with recombinant expanded vs. wild-type PABPN1; immunofluorescence in OPMD patient muscle; molecular dynamics simulations PloS one Medium 19641605
2012 Nuclear speckles serve as biogenesis sites for PABPN1 intranuclear inclusions; growing inclusions progressively deplete PABPN1 and poly(A) RNA from speckles, disrupting post-transcriptional processing capacity. Time-lapse imaging of GFP-PABPN1 in human myoblasts; immunofluorescence in OPMD patient muscle biopsies Neurobiology of disease Medium 22249111
2013 PABPN1 negatively autoregulates its own expression by binding to an adenosine-rich region in its 3' UTR, promoting retention of the 3'-terminal intron and subsequent clearance of intron-retained pre-mRNA by the nuclear exosome (Rrp6-dependent pathway). Intron retention analysis by RT-PCR; PABPN1 overexpression/knockdown in human cells; nuclear exosome subunit knockdown; RNA immunoprecipitation Molecular and cellular biology High 25963658
2013 PABPN1 opposes Nab2 in nuclear poly(A)-binding protein interplay: Pab2 (PABPN1 ortholog in fission yeast) promotes nuclear pre-mRNA decay via Rrp6, while Nab2 competes with Pab2 for polyadenylated transcripts to stabilize them. Genetic and biochemical analysis in S. pombe; Pab2 and Nab2 deletion strains; mRNA decay assays; competitive binding experiments Molecular and cellular biology Medium 24081329
2013 A proline-tyrosine nuclear localization signal (PY-NLS) is required for nuclear import of fission yeast Pab2 via karyopherin Kap104, but a functional PY-NLS is not required for nuclear entry of human PABPN1, suggesting alternative or redundant import pathways exist for human PABPN1. NLS mutagenesis; karyopherin binding assays with recombinant proteins; nuclear localization assays in S. pombe and human cells Traffic (Copenhagen, Denmark) Medium 23279110
2014 ARIH2 E3-ubiquitin ligase regulates PABPN1 protein accumulation and aggregation; PABPN1 in turn controls ARIH2 mRNA levels via alternative polyadenylation site usage, forming a feed-forward regulatory loop relevant to aging-associated muscle degeneration. Knockdown/overexpression of ARIH2 and PABPN1 in muscle cells; antisense oligonucleotides masking proximal PAS in ARIH2 3' UTR; protein accumulation and aggregation assays; in vivo mRNA quantification in mouse muscles The American journal of pathology Medium 24486325
2015 PABPN1 promotes splicing of a subset of introns that are excised after polyadenylation; this splicing-stimulatory function requires PABPN1's RNA-binding activity and, to a lesser extent, its poly(A) polymerase (PAP)-stimulatory function, and operates in the context of the terminal poly(A) tail rather than internal A-tracts. PABPN1 depletion by RNAi in human cells; splicing assays; recruitment of splicing factors monitored by chromatin immunoprecipitation; domain mutant complementation Molecular and cellular biology High 25896913
2017 PABPN1 interacts with Matrin 3 (MATR3) in mouse skeletal muscle; both proteins co-regulate alternative polyadenylation, intron retention, and levels of lncRNA Neat1; together they are required for normal paraspeckle function and adenosine-to-inosine RNA editing of Ctn RNA in muscle cells. Co-immunoprecipitation from mouse skeletal muscle followed by mass spectrometry; knockdown of MATR3 and PABPN1; RNA editing and APA analysis; paraspeckle immunofluorescence in OPMD mouse model Nucleic acids research High 28977530
2017 CircPABPN1 (hsa_circ_0031288, arising from PABPN1 pre-mRNA) sequesters HuR, preventing HuR from binding to PABPN1 mRNA and thereby suppressing PABPN1 translation; HuR positively regulates PABPN1 translation, and CircPABPN1 negatively regulates it by competitive binding. HuR-RIP followed by circRNA sequencing; CircPABPN1 overexpression/knockdown; PABPN1 mRNA polysome analysis; RIP of HuR on PABPN1 mRNA RNA biology High 28080204
2018 HuR binds to cis-regulatory elements in the Pabpn1 3' UTR and negatively regulates Pabpn1 mRNA stability and hence PABPN1 protein levels specifically in mature skeletal muscle in vitro and in vivo. RNA immunoprecipitation; HuR overexpression/knockdown in C2C12 myotubes and primary muscle cells; in vivo mouse experiments; mRNA decay assays Nucleic acids research Medium 29939290
2019 Reduced PABPN1 levels cause elevated SIRT1 deacetylase activity (via alternative polyadenylation-mediated increase in SIRT1 mRNA); SIRT1 inhibition by sirtinol increases PABPN1 levels and reverses muscle wasting, establishing a regulatory loop between PABPN1-mediated APA and SIRT1 deacetylase. Transcriptomic and proteomic comparison of shPABPN1 vs. control mouse muscles; acetylome profiling; sirtinol pharmacological inhibition; western blotting iScience Medium 30739015
2019 PABPN1 localizes to mitochondria in OPMD patient muscle; both wild-type (10-ala) and expanded (18-ala) PABPN1 accumulate in mitochondria and interact with the TIM23 mitochondrial protein import complex, but the expanded form decreases cell viability and forms aggresomes. Immunolocalization in OPMD patient muscle; fractionation and co-immunoprecipitation with TIM23 in cell models expressing 10-ala and 18-ala PABPN1; cell viability assays Laboratory investigation Medium 30894671
2020 PABPN1 is necessary for p63α mRNA translation by modulating binding of translation initiation factors eIF4E and eIF4G to p63α mRNA; PABPN1 also controls alternative polyadenylation of p63 pre-mRNA in coding sequence, and p63α (downstream of p53 family) transcriptionally regulates PABPN1, forming a feedback loop. PABPN1 knockdown in HaCaT keratinocytes; polysome analysis; eIF4E/eIF4G RNA immunoprecipitation; APA analysis; luciferase reporter for PABPN1 promoter The Journal of investigative dermatology Medium 32243883
2022 PABPN1 promotes the formation of nuclear poly(A) domains (NPADs) in mouse oocytes through liquid-liquid phase separation mediated by its N-terminal disordered domain and RNA recognition motif; loss of PABPN1 abolishes NPAD formation, destabilizes oocyte-growth transcripts, and causes female sterility. Pabpn1 conditional knockout in mouse oocytes; live imaging of NPAD; domain deletion analysis of phase separation; transcript stability assays; fertility phenotyping Science advances High 36306357
2022 Cytoplasmic PABPN1 mediates zygotic genome activation-dependent maternal mRNA clearance (Z-decay) in mouse embryos: it docks on 3'-uridylated transcripts downstream of TUT4/TUT7 and recruits the 3'-5' exoribonuclease DIS3L2, facilitating mRNA decay; Pabpn1 knockout causes developmental arrest at morula stage. Pabpn1 knockout mice; RNA immunoprecipitation; uridylation assays; DIS3L2 co-immunoprecipitation; transcriptome analysis of maternal mRNA clearance Nucleic acids research High 34904664
2023 The poly(A) tail acts as a splicing enhancer for last introns via PABPN1 in HeLa cells; PABPN1 depletion causes retention of introns with weak 3' splice sites located near the 3' end; PABPN1 recruits RBM26/RBM27 (via interaction with the coiled-coil and RRM domain of RBM27) to promote terminal intron splicing. PABPN1 knockdown followed by RNA-seq; tethering of PABPN1 to non-polyadenylated transcripts; TurboID proximity labeling-MS for PABPN1 interactome; co-immunoprecipitation of RBM27; conservation analysis in mice EMBO reports High 37661812
2024 SNRPD2 interacts with the glutamic-proline (EP) domain of PABPN1 and disrupts PABPN1 liquid-liquid phase separation (LLPS), reducing suppression of proximal poly(A) sites and causing shortened 3' UTRs (APA shift) that promote colorectal cancer cell proliferation and migration. APA profiling; LLPS assays; co-immunoprecipitation of SNRPD2 with PABPN1; domain mutagenesis; functional cancer cell assays Science China. Life sciences Medium 38811444

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1. RNA biology 697 28080204
1998 Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. Nature genetics 625 9462747
2005 The MexGHI-OpmD multidrug efflux pump controls growth, antibiotic susceptibility and virulence in Pseudomonas aeruginosa via 4-quinolone-dependent cell-to-cell communication. Microbiology (Reading, England) 170 15817779
2002 Characterization of a new efflux pump, MexGHI-OpmD, from Pseudomonas aeruginosa that confers resistance to vanadium. Microbiology (Reading, England) 141 12177331
2001 Oligomerization of polyalanine expanded PABPN1 facilitates nuclear protein aggregation that is associated with cell death. Human molecular genetics 101 11689481
2013 PABPN1: molecular function and muscle disease. The FEBS journal 96 23601051
2005 An essential cytoplasmic function for the nuclear poly(A) binding protein, PABP2, in poly(A) tail length control and early development in Drosophila. Developmental cell 84 16198293
2006 A Drosophila model of oculopharyngeal muscular dystrophy reveals intrinsic toxicity of PABPN1. The EMBO journal 76 16642034
2009 Bortezomib induces the formation of nuclear poly(A) RNA granules enriched in Sam68 and PABPN1 in sensory ganglia neurons. Neurotoxicity research 67 19609631
2003 Functional cloning and characterization of a multidrug efflux pump, mexHI-opmD, from a Pseudomonas aeruginosa mutant. Antimicrobial agents and chemotherapy 66 12937010
2000 The nuclear poly(A) binding protein, PABP2, forms an oligomeric particle covering the length of the poly(A) tail. Journal of molecular biology 66 10731412
2017 Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing. Nucleic acids research 62 28977530
2015 Regulated Intron Retention and Nuclear Pre-mRNA Decay Contribute to PABPN1 Autoregulation. Molecular and cellular biology 61 25963658
2005 In vivo aggregation properties of the nuclear poly(A)-binding protein PABPN1. RNA (New York, N.Y.) 59 15811916
2005 PABPN1 overexpression leads to upregulation of genes encoding nuclear proteins that are sequestered in oculopharyngeal muscular dystrophy nuclear inclusions. Neurobiology of disease 58 15755682
2000 Nuclear accumulation of expanded PABP2 gene product in oculopharyngeal muscular dystrophy. Muscle & nerve 58 11003790
2017 PABPN1 gene therapy for oculopharyngeal muscular dystrophy. Nature communications 56 28361972
2003 Myopathy phenotype in transgenic mice expressing mutated PABPN1 as a model of oculopharyngeal muscular dystrophy. Human molecular genetics 52 14645203
2008 Sirtuin inhibition protects from the polyalanine muscular dystrophy protein PABPN1. Human molecular genetics 51 18397876
2016 Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy. Neurology 50 28011929
2003 Trinucleotide expansions leading to an extended poly-L-alanine segment in the poly (A) binding protein PABPN1 cause fibril formation. Protein science : a publication of the Protein Society 49 14627730
2019 Delivery of mesenchymal stem cells-derived extracellular vesicles with enriched miR-185 inhibits progression of OPMD. Artificial cells, nanomedicine, and biotechnology 48 31219352
2013 A decline in PABPN1 induces progressive muscle weakness in oculopharyngeal muscle dystrophy and in muscle aging. Aging 47 23793615
2003 HnRNP A1 and A/B interaction with PABPN1 in oculopharyngeal muscular dystrophy. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 46 12945950
2005 Induction of HSP70 expression and recruitment of HSC70 and HSP70 in the nucleus reduce aggregation of a polyalanine expansion mutant of PABPN1 in HeLa cells. Human molecular genetics 43 16239242
2000 Localization of poly(A)-binding protein 2 (PABP2) in nuclear speckles is independent of import into the nucleus and requires binding to poly(A) RNA. Journal of cell science 43 10825302
2003 Nuclear poly(A)-binding protein PABPN1 is associated with RNA polymerase II during transcription and accompanies the released transcript to the nuclear pore. Experimental cell research 42 12749861
2000 Oculopharyngeal MD among Bukhara Jews is due to a founder (GCG)9 mutation in the PABP2 gene. Neurology 41 11087766
2017 Novel mouse models of oculopharyngeal muscular dystrophy (OPMD) reveal early onset mitochondrial defects and suggest loss of PABPN1 may contribute to pathology. Human molecular genetics 40 28575395
2011 Deregulation of the ubiquitin-proteasome system is the predominant molecular pathology in OPMD animal models and patients. Skeletal muscle 40 21798095
2015 Poly(A) Polymerase and the Nuclear Poly(A) Binding Protein, PABPN1, Coordinate the Splicing and Degradation of a Subset of Human Pre-mRNAs. Molecular and cellular biology 39 25896913
2005 Oculopharyngeal muscular dystrophy (OPMD): analysis of the PABPN1 gene expansion sequence in 86 patients reveals 13 different expansion types and further evidence for unequal recombination as the mutational mechanism. Human genetics 39 15645184
2022 PABPN1 functions as a hub in the assembly of nuclear poly(A) domains that are essential for mouse oocyte development. Science advances 38 36306357
2009 Hsp70 chaperones and type I PRMTs are sequestered at intranuclear inclusions caused by polyalanine expansions in PABPN1. PloS one 38 19641605
2008 Wild-type PABPN1 is anti-apoptotic and reduces toxicity of the oculopharyngeal muscular dystrophy mutation. Human molecular genetics 38 18178579
2005 Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in mice. Neurobiology of disease 37 15755680
2016 PABPN1-Dependent mRNA Processing Induces Muscle Wasting. PLoS genetics 36 27152426
2011 Antiprion drugs 6-aminophenanthridine and guanabenz reduce PABPN1 toxicity and aggregation in oculopharyngeal muscular dystrophy. EMBO molecular medicine 36 21204267
2007 Soluble expanded PABPN1 promotes cell death in oculopharyngeal muscular dystrophy. Neurobiology of disease 34 17418585
2022 Nuclear poly(A) binding protein 1 (PABPN1) mediates zygotic genome activation-dependent maternal mRNA clearance during mouse early embryonic development. Nucleic acids research 33 34904664
2013 Control of mRNA stability contributes to low levels of nuclear poly(A) binding protein 1 (PABPN1) in skeletal muscle. Skeletal muscle 33 24083404
2008 PABPN1 polyalanine tract deletion and long expansions modify its aggregation pattern and expression. Experimental cell research 33 18367172
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