| 2015 |
PTBP1 represses Pbx1 exon 7 splicing in embryonic stem cells, suppressing expression of the neuronal Pbx1a isoform; CRISPR-Cas9 deletion of exon 7 regulatory elements induced Pbx1a expression and activated neuronal gene transcription, establishing PTBP1 as a controller of the Pbx1 transcriptional program during early neuronal development. |
CRISPR-Cas9 regulatory element deletion, alternative splicing analysis, transcriptional reporter assays in ESCs and NPCs |
eLife |
High |
26705333
|
| 2016 |
PTBP1 and PTBP2 display similar RNA-binding profiles across the transcriptome (shown by knockin replacement of Ptbp2 with Ptbp1), yet exhibit distinct splicing outcomes for many neuronal exons, indicating that differential cofactor interactions rather than differential RNA binding underlie their distinct regulatory networks. |
Conditional knockin mouse (Ptbp1 replacing Ptbp2), transcriptome-wide eCLIP/RNA-seq comparison, Ptbp2 knockout rescue experiments |
Cell reports |
High |
27926877
|
| 2015 |
PTBP1 and RBFOX proteins regulate the alternative splicing of micro-exons (≤51 nt) in human brain transcripts; PTBP1 binding adjacent to intronic sequences suppresses micro-exon inclusion, while RBFOX proteins promote inclusion in brain, muscle, and heart. |
Genomic deep-sequencing analysis of micro-exon splicing coupled with splicing factor binding data (CLIP-seq datasets) |
Genome research |
Medium |
25524026
|
| 2011 |
PTBP1 binds an intronic polypyrimidine sequence downstream of USP5 exon 15 and promotes generation of a shorter USP5 isoform 2 in glioblastoma; PTBP1 knockdown shifted splicing toward isoform 1 and inhibited GBM cell growth and migration. |
Affymetrix exon arrays, PTBP1 siRNA knockdown, antisense oligonucleotide splicing modulation, cell growth/migration assays |
Molecular carcinogenesis |
Medium |
21976412
|
| 2016 |
PTBP1 promotes PKM2 isoform expression by controlling alternative splicing of the PKM gene, thereby enhancing the Warburg effect in colorectal cancer; miR-1 and miR-133b suppress this pathway by silencing PTBP1 and switching PKM isoform expression from PKM2 to PKM1. |
Ectopic miRNA expression, PKM isoform RT-PCR, in vitro and in vivo growth assays, ROS measurement |
Oncotarget |
Medium |
26980745
|
| 2016 |
PTBP1 regulates alternative splicing of cortactin exon 11; knockdown of PTBP1 causes exclusion of exon 11 and reduces cortactin isoform-a expression, which decreases colorectal cancer cell migration and invasion; overexpression of cortactin isoform-a rescues the PTBP1-knockdown motility phenotype. |
siRNA knockdown, RT-PCR isoform analysis, cell migration/invasion assays, in vivo shRNA tumor model, rescue overexpression |
Oncotarget |
Medium |
28404950
|
| 2016 |
PTBP1 binds MCL1 mRNA and destabilizes it; PTBP1 knockdown increases MCL1 mRNA stability and cytoplasmic accumulation, elevating MCL1 protein and protecting cancer cells from antitubulin-induced apoptosis in an MCL1-dependent manner. |
RNA immunoprecipitation, mRNA stability assays, siRNA knockdown, MCL1-dependent apoptosis rescue experiments |
Cell death and differentiation |
Medium |
27367564
|
| 2018 |
PTBP1 enhances miR-101-guided AGO2 targeting to MCL1 mRNA, facilitating miR-101-induced apoptosis and clonogenic inhibition; PTBP1 coordinates with miRISC on a shared target mRNA. |
RNA immunoprecipitation of AGO2, functional co-knockdown/overexpression assays, clonogenic survival assays |
Cell death & disease |
Medium |
29748555
|
| 2018 |
PTBP1 enhances CCND3 mRNA translation by binding its 5'-UTR, promoting cell cycle progression and tumor growth in hepatocellular carcinoma; miR-194 represses PTBP1 by binding its 3'-UTR, reducing CCND3 levels. |
RNA immunoprecipitation, luciferase 5'-UTR reporter assay, polysome fractionation, miRNA target validation |
The Journal of pathology |
Medium |
31301177
|
| 2018 |
NOVA1 directs PTBP1 to hTERT pre-mRNA in a NOVA1-dependent fashion (shown by RNA pulldown); PTBP1 promotes full-length hTERT splicing and telomerase activity, while its knockdown reduces telomerase activity and leads to progressive telomere shortening. |
RNA pulldown, PTBP1 stable knockdown, telomerase activity assay (TRAP), telomere length measurement |
Oncogene |
Medium |
30568224
|
| 2019 |
PTBP1 binds to polypyrimidine sequences on both upstream intron 11 and downstream intron 11a of the Mena pre-mRNA (confirmed by RNA pulldown and mutation analysis), promoting Mena exon 11a skipping; this skipping is required for PTBP1-driven lung cancer cell migration and invasion, and is reversed by MenaΔ11a overexpression. |
RNA pulldown with mutational analysis of binding sites, shRNA KD, overexpression rescue, migration/invasion assays |
Biochimica et biophysica acta. Gene regulatory mechanisms |
Medium |
31075540
|
| 2019 |
PTBP1 binds SLC31A1 mRNA via RIP-confirmed interaction and reduces SLC31A1 mRNA stability, thereby decreasing copper transporter expression; PTBP1 knockdown upregulates SLC31A1 and enhances cisplatin sensitivity in chemoresistant osteosarcoma cells. |
RNA immunoprecipitation, dual-luciferase reporter assay, RNA stability (actinomycin D chase), siRNA knockdown, xenograft model |
Journal of cellular and molecular medicine |
Medium |
32207235
|
| 2019 |
PTBP1 binds the precursors of let-7a-1 and let-7d miRNAs (shown by RNA pulldown and RIP) and suppresses their maturation; lncRNA H19 reduces PTBP1 levels, thereby relieving this suppression and promoting let-7 biogenesis in cholestasis. |
RNA pulldown, RNA immunoprecipitation (RIP), miRNA precursor quantification, BDL mouse model, H19 KO |
Cell death & disease |
Medium |
30778047
|
| 2019 |
PTBP1 acts as a splicing enhancer for CD33 exon 2 inclusion; PTBP1 binds RNA sequences proximal to the intron 1-exon 2 splice junction, and this binding is altered by the Alzheimer's disease-associated SNP, providing a mechanism for SNP-dependent alternative splicing of CD33. |
Functional genomics splicing assays, proteomic PTBP1 identification, RNA binding site analysis by mutagenesis near SNP |
Molecular and cellular biology |
Medium |
31208978
|
| 2019 |
hnRNP I (PTBP1 ortholog in zebrafish) destabilizes the Notch intracellular domain (NICD) and inhibits Notch signaling; this function requires the C-terminal RAM domain of NICD and is conserved from zebrafish to human, regulating intestinal epithelial homeostasis. |
Zebrafish mutant (brom bones), overexpression in zebrafish and human cells, co-IP/biochemistry with NICD, Notch target gene analysis |
PLoS genetics |
Medium |
19197356
|
| 2019 |
TCF3 mutually exclusive alternative splicing is regulated by PTBP1 binding to conserved intronic splicing silencers (ISSs) between the two mutually exclusive exons; PTBP1 and hnRNPH1 act cooperatively through position-dependent interactions at ISSs and ESSs to control TCF3 exon 18a/18b selection. |
ISS mutagenesis, PTBP1 and hnRNPH1 co-knockdown/overexpression, splicing reporter assays |
RNA (New York, N.Y.) |
Medium |
31391218
|
| 1997 |
A 60-amino-acid sequence at the amino terminus of hnRNP I/PTBP1 (designated NLD-I) is both necessary and sufficient for nuclear localization, representing a novel bipartite nuclear localization signal distinct from canonical NLS sequences in other hnRNP proteins. |
CAT reporter fusion constructs, transient transfection localization assay |
Experimental cell research |
Medium |
9281380
|
| 2020 |
LUCAT1 lncRNA interacts with PTBP1 in colorectal cancer cells and facilitates association of PTBP1 with DNA damage-related gene pre-mRNAs, altering their alternative splicing and contributing to chemotherapy resistance; PTBP1 overexpression rescues LUCAT1 knockdown phenotypes. |
RNA pulldown, RNA immunoprecipitation, RNA-seq of alternative splicing, rescue overexpression, in vivo ASO experiments |
Molecular cancer |
Medium |
31964396
|
| 2020 |
SINEUP lncRNAs require PTBP1 and HNRNPK for their sub-cellular distribution and for assembly of translational initiation complexes; these RBPs promote co-localization of SINEUP RNA with target mRNAs in the cytoplasm and enhance target mRNA translation. |
Co-transfection, subcellular fractionation, translational initiation complex assembly assays, RBP knockdown |
Nucleic acids research |
Medium |
33130894
|
| 2021 |
SON acts as a master regulator of PTBP1-mediated oncogenic splicing in glioblastoma: SON knockdown causes failure of intron removal from the PTBP1 transcript, leading to PTBP1 downregulation; SON also forms a complex with hnRNP A2B1 to suppress RBFOX2-mediated neuronal splicing, including skipping of the PTBP2 neuronal exon. |
SON knockdown (siRNA/shRNA), PTBP1/PTBP2 mRNA/protein analysis, hnRNP A2B1 co-IP, GBM xenograft model |
Nature communications |
Medium |
34548489
|
| 2022 |
MALAT1 lncRNA stabilizes the interaction between PTBP1 and PSF, forming a functional tripartite module that regulates a network of alternative splicing events; MALAT1 also stabilizes PSF interactions with several other hnRNP proteins. |
RNA immunoprecipitation, co-IP (PTBP1-PSF interaction with/without MALAT1), alternative splicing RNA-seq, functional knockdown |
Science advances |
Medium |
36563164
|
| 2023 |
PTBP1-associated RNA loops within individual introns preferentially promote cassette exon splicing by accelerating asymmetric intron removal, while loops spanning across cassette exons repress splicing; these positional rules predict PTBP1-regulated splicing outcomes genome-wide. |
Capture RIC-seq (CRIC-seq) method for PTBP1-associated in situ proximal RNA-RNA contacts in HeLa cells, combined with splicing analysis |
Molecular cell |
High |
36958328
|
| 2023 |
Integrative structural analysis (NMR, mass spectrometry, small-angle scattering) determined the solution structure of PTBP1 bound to an RNA fragment from the EMCV IRES; PTBP1 acts as an RNA chaperone orchestrating the IRES RNA into a few distinct compact conformations with RNA stems exposed outward, maintaining conformational flexibility. |
Magnetic resonance (NMR), mass spectrometry, small-angle X-ray/neutron scattering (SAXS/SANS), integrative structural modeling |
Nature communications |
High |
37833274
|
| 2018 |
Mass spectrometry identified distinct phosphorylation and acetylation modifications on PTBP1 versus PTBP2; PTBP1 has unique phosphorylation sites in its N-terminal, linker 1, and linker 2 regions, and distinct acetylation sites in RRM2 and RRM3, suggesting PTMs contribute to their differential splicing activities. |
Mass spectrometry of PTMs on proteins from in vitro splicing reactions |
Biochemistry |
Medium |
29851470
|
| 2022 |
PTBP1 interacts with distinct protein partners compared to PTBP2 under in vitro splicing conditions; PTBP1 uniquely associates with many mRNA processing and splicing regulatory proteins, while both paralogs interact with chromatin remodeling factors; potential PTM writers/erasers differ between the paralogs. |
In vitro splicing conditions, co-immunoprecipitation, mass spectrometry-based interactome |
PloS one |
Medium |
35113929
|
| 2019 |
PTBP1 mRNA isoforms differ in their 5'-UTR and 3'-UTR sequences; eIF3 binds each isoform differently in a cell cycle-dependent manner and binding correlates with repression of PTBP1 protein during S phase, demonstrating translational regulation of PTBP1 expression during the cell cycle. |
PTBP1 mRNA isoform mapping in HEK293T cells, eIF3 RIP, cell cycle synchronization, western blot |
RNA (New York, N.Y.) |
Medium |
31263002
|
| 2022 |
PTBP1 is required for endothelial NF-κB priming under low and disturbed blood flow (LDF); PTBP1 deletion reverses LDF-induced RNA splicing patterns, inhibits NF-κB nuclear translocation, and reduces ICAM1/VCAM1 induction by TNF-α; in vivo endothelial-specific Ptbp1 deletion reduced ICAM1 expression, myeloid infiltration, and atherosclerotic plaque in LDF regions; a mechanism involves altered splicing of Ripk1 (cassette exon inclusion reducing Ripk1 protein). |
CRISPR Cas9 KO screen, endothelial-specific conditional KO mouse, LDF model, NF-κB nuclear translocation assay, ICAM1/VCAM1 induction, Ripk1 splicing analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
35858420
|
| 2023 |
Endothelial-specific knockout of Ptbp1 in mice causes left ventricular noncompaction by reducing endothelial cell migration, disrupting cardiomyocyte proliferation; mechanistically, Ptbp1 deletion alters alternative splicing of β-arrestin-1 (Arrb1), which affects endothelial cell migration. |
Endothelial-specific conditional Ptbp1 knockout mouse, ventricular morphology analysis, endothelial cell migration assay, Arrb1 splicing analysis |
Nature communications |
High |
37002228
|
| 2019 |
B-cell-specific Ptbp1 deletion impairs BCR-mediated B-cell activation and plasmablast generation, resulting in defective antibody production against T-cell-independent and T-cell-dependent antigens, demonstrating Ptbp1 is essential for the humoral immune response. |
B-cell-specific conditional Ptbp1 knockout mouse, NP-Ficoll and NP-CGG immunization, antibody titer measurement, plasmablast FACS |
International immunology |
High |
30476084
|
| 2021 |
In dendritic cells, Ptbp1 deletion increases MHC II expression and perturbs T-cell homeostasis without affecting DC development; PTBP1 regulates alternative splicing of Pkm and a subset of interferon-response genes in DCs, and its deletion enhances antitumor immunity. |
DC-specific Ptbp1 conditional KO mouse, MHC II FACS, T-cell homeostasis analysis, alternative splicing RNA-seq, tumor challenge model |
Immunology |
Medium |
33421118
|
| 2023 |
PTBP1 is expressed in adult sensory and motor neurons (not only embryonic neurons); axonal PTBP1 levels increase markedly after peripheral nerve injury, where it associates with injury-response mRNAs (including KPNB1/importin β1 and RHOA); perturbation of PTBP1 affects local axonal translation, nociceptor regeneration, and thermal/mechanical sensation. |
Immunofluorescence/fractionation for subcellular localization, RNA-protein co-IP in axons, PTBP1 perturbation with sensory behavioral readouts, nerve injury model |
Science advances |
Medium |
37506203
|
| 2025 |
PTBP1 is lactylated at K436 in glioma stem cells; SIRT1 acts as the delactylase. K436 lactylation inhibits PTBP1 proteasomal degradation by attenuating interaction with the E3 ligase TRIM21, and enhances PTBP1 RNA-binding capacity to stabilize PFKFB4 mRNA, driving glycolysis in a feedforward loop. |
Lactylation proteomics, K436 site-directed mutagenesis, co-IP (PTBP1-TRIM21), ubiquitination assay, SIRT1 delactylase assay, PFKFB4 mRNA stability assay, GSC functional assays |
Cancer research |
High |
39570804
|
| 2024 |
PTBP1 is crotonylated at K266 by KAT2B in colorectal cancer; K266 crotonylation enhances PTBP1 interaction with hnRNPA1/A2, promoting PKM2 isoform expression over PKM1 through alternative splicing, thereby increasing glycolysis and CRC progression. |
Crotonylation proteomics, K266 site mutagenesis, co-IP (PTBP1-hnRNPA1/2), PKM isoform RT-PCR, glycolysis assays, KAT2B identification, CRC xenograft model |
Journal of translational medicine |
High |
39497094
|
| 2022 |
The deubiquitinating enzyme PSMD14 interacts with PTBP1 (confirmed by co-IP), promotes PTBP1 deubiquitination, and stabilizes PTBP1 protein; PSMD14 knockdown reduces PTBP1 protein levels and inhibits gastric cancer cell proliferation and invasion. |
Co-immunoprecipitation, ubiquitination assay, PSMD14 and PTBP1 co-localization, siRNA knockdown, in vitro and in vivo functional assays |
Experimental cell research |
Medium |
35405117
|
| 2024 |
PTBP1 interacts with RALY (hnRNP associated with lethal yellow protein homolog) and together they regulate exon 5 splicing of DNMT3B, shifting from the DNMT3B-S to DNMT3B-L isoform; DNMT3B-L promotes promoter methylation of DUSP2, inhibiting its expression and enhancing radioresistance in prostate cancer. |
Co-IP (PTBP1-RALY), splicing minigene assays, DNMT3B isoform RT-PCR, DUSP2 promoter methylation (bisulfite sequencing/ChIP), KD/OE functional assays, irradiation experiments in vitro and in vivo |
Advanced science |
Medium |
39287090
|
| 2024 |
USP46 deubiquitinates PTBP1 and stabilizes it by inhibiting K48-linked ubiquitin-mediated degradation; stabilized PTBP1 increases the PKM2/PKM1 ratio, promoting glycolysis and tamoxifen resistance in breast cancer cells. |
Co-IP (USP46-PTBP1), K48-linked ubiquitination assay, PKM isoform ratio analysis, glycolysis assay, siRNA KD functional assays |
Biochimica et biophysica acta. Molecular basis of disease |
Medium |
38176460
|
| 2014 |
PTBP1 represses inclusion of ABLIM1 exon 11 in skeletal muscle; in a cellular splicing assay, PTBP1 acts together with CELF proteins and MBNL proteins to regulate this exon, and ABLIM1 exon 11 is aberrantly excluded in DM1 patients consistent with PTBP1 activity. |
Cellular splicing reporter assay, patient tissue RT-PCR, transfection overexpression |
Genes to cells |
Medium |
25403273
|
| 2023 |
CTC-490G23.2 lncRNA acts as a scaffold to increase PTBP1 binding to CD44 pre-mRNA, causing a splicing switch from CD44s to CD44v(8-10); CD44v(8-10) binds vimentin and increases its protein stability, promoting cancer metastasis. |
RNA pulldown, RIP, CD44 isoform RT-PCR, vimentin co-IP with CD44 isoforms, invasion/metastasis assays in vitro and in vivo |
Oncogene |
Medium |
36792757
|
| 2024 |
lncRNA DCRT directly binds PTBP1 in the nucleus of cardiomyocytes (shown by RIP and chromatin coIP) and inhibits PTBP1-mediated skipping of NDUFS2 exon 3; exon 3 skipping impairs mitochondrial complex I activity and disrupts PRDX5 antioxidant function, causing cardiomyopathy. |
RNA immunoprecipitation, DCRT KO mice (CRISPR-Cas9), NDUFS2 isoform sequencing, mitochondrial complex I activity assay, cardiac function phenotyping |
Circulation |
High |
38841852
|
| 2020 |
PTBP1 participates with RBM20 in regulating alternative splicing of FHOD3 exons in cardiac tissue; co-expression of RBM20 and PTBP1 promotes alternative shift from exon inclusion to exclusion, affecting actin filament organization by FHOD3 isoforms. |
RT-PCR splicing analysis, PTBP1 and RBM20 overexpression in cells, FHOD3 isoform quantification in human tissues |
The international journal of biochemistry & cell biology |
Medium |
30468920
|
| 2021 |
MALAT1 lncRNA is m6A-methylated by METTL3, promoting MALAT1 upregulation; MALAT1 interacts with PTBP1 to promote degradation of USP8 mRNA, reducing USP8 expression; reduced USP8 promotes TAK1 ubiquitination and protein instability, activating pyroptosis and M1 macrophage polarization to aggravate liver fibrosis. |
m6A MeRIP, RNA pulldown, RIP, RNA stability assay, co-IP (USP8-TAK1 ubiquitination), gain/loss-of-function, liver fibrosis mouse model |
Cell death discovery |
Medium |
34839365
|
| 2005 |
Xenopus hnRNP I (PTBP1 ortholog) interacts with 40LoVe at the VM1 motif of the Vg1 localization element, forming a localization RNP complex; 40LoVe also interacts with Vg1RBP/Vera at the E2 motif; in vivo titration indicates VM1- and E2-binding proteins have distinct roles in Vg1LE-dependent mRNA localization. |
Co-immunoprecipitation, RNA localization element binding competition assays in Xenopus oocytes |
RNA (New York, N.Y.) |
Medium |
16373488
|
| 2020 |
Charme lncRNA nuclear isoform (pCharme) interacts with PTBP1 and MATR3 through sequences within its alternatively spliced intron-1; CRISPR-Cas9 deletion of intron-1 releases pCharme from chromatin and causes cardiac defects similar to full-length Charme knockout, demonstrating PTBP1 is required for pCharme chromatin anchoring during myogenesis. |
RNA antisense purification (RAP) with mass spectrometry, CRISPR-Cas9 intron-1 deletion, chromatin fractionation, cardiac phenotyping in mice |
Cell reports |
Medium |
33357424
|
| 2023 |
PTBP1 directly interacts with c-Myc protein and stabilizes its protein levels by preventing proteasomal degradation; this is mediated by upregulation of USP28 and limitation of FBW7-mediated c-Myc ubiquitination; PTBP1 depletion-induced tumor regression is rescued by exogenous c-Myc expression. |
Co-immunoprecipitation (PTBP1-c-Myc), ubiquitination assay, USP28/FBW7 expression analysis, rescue overexpression, in vivo xenograft |
British journal of cancer |
Medium |
36635500
|