PABPN1 effect on translation efficiency.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE165609 | GEO | 2022/05/17
REPOSITORIES: GEO
Similar Datasets
Project description:PABPN1 effect on translation efficiency.
| PRJNA695208 | ENA
Project description:To identify mRNAs that are most translationally repressed following eIF4A inhibition and those that are relatively insensitive, polysome profiling was carried with and without eIF4A inhibition by hippuristanol treatment. Polysomal, sub-polysomal and total RNA was sequenced and we used a Bayesian model to identify mRNAs that with greatest confidence had shifted from the polysomal into the sub-polysomal fractions, from the sub-polysomal into the polysomal fractionsand those mRNAs that did not change in their polysomal to sub-polysomal ratio, following hipp treatment, which were termed eIF4A-dependent, eIF4A-antidependent and eIF4A-independent mRNAs respectively
2019-11-21 | GSE134888 | GEO
Project description:Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset syndrome characterized by progressive degeneration of particular muscles. OPMD is caused by short GCG repeat expansions within the gene encoding the nuclear poly(A)-binding protein 1 (PABPN1) that extend an N-terminal polyalanine tract in the protein. Mutant PABPN1 aggregates as nuclear inclusions in OMPD patient muscles. We have created a Drosophila model of OPMD that recapitulates the features of the human disorder: progressive muscle degeneration, with muscle defects proportional to the number of alanines in the tract, and formation of PABPN1 nuclear inclusions. Wild-type human PABPN1 contains a stretch of 10 alanines following the initial methionine, which is expanded to 12–17 alanines in OPMD patients. In Drosophila, the PABPN1 homolog is the poly(A)-binding protein 2 (PABP2), which has the same function as PABPN1 in nuclear polyadenylation but lacks a polyalanine tract at the N-terminus. We used the UAS/Gal4 system to express mammalian PABPN1 in Drosophila. An alanine-expanded PABPN1 cDNA (encoding the 17 alanine tract) was cloned downstream of UAS sequences (UAS-PABPN1). Transgenic lines containing this construct were crossed to a Mhc-Gal4 driver, leading to muscle-specific expression. To gain insight into the molecular and physiological defects in OPMD we performed a transcriptomic analysis in OPMD fly muscles. Using microarrays, thorax gene expression was compared between control flies (Mhc-Gal4/+) and flies expressing PABPN1-17ala in thoracic muscles (UAS-PABPN1-17ala/+; Mhc-Gal4/+), at three time points (days 2, 6 and 11). Transcriptome of thorax RNA samples from control (Mhc-Gal4/+) flies and flies expressing PABPN1-17ala (UAS-PABPN1-17ala/+; Mhc-Gal4/+)
2014-12-12 | GSE64094 | GEO
Project description:Poly(A) binding protein nuclear 1 (PABPN1) is a multifunctional regulator of mRNA processing. PABPN1 inhibits alternative polyadenylation (APA), and in conditions with reduced PABPN1 levels APA utilization causes genome-wide mRNA dysregulation. PABPN1 levels decline from midlife onwards in Oculopharyngeal Muscular Dystrophy (OPMD) and in aged muscles. Reduced PABPN1 levels cause muscle atrophy by altering mRNA levels of the ubiquitin proteasome system. The effect of PABPN1-mediated APA utilization on the proteome has not been investigated yet. We report the PABPN1-mediated proteome in Tibialis anterior (TA) mouse muscles, signifying functional impact for the mitochondria, cytoskeleton and translation cellular machineries. Central nucleation and split myofibers marked PABPN1-derived muscle histology. We show that up-regulation of the cytoskeletal proteins: Murc, Pfn1 and Csrp3, is highly associated with PABPN1-mediated muscle pathology and with reduced PABPN1 levels. Elevation of PABPN1 levels by sirtinol treatment reversed muscle pathology and restored levels of those cytoskeletal proteins. We suggest that restoration of PABPN1 levels in aged muscles could be a novel therapeutic strategy to mitigate muscle waste.
2020-07-06 | PXD004865 | Pride
Project description:Here, we present a 3'-Seq dataset of Pabpn1 KD LK cells and Scr control cells.
2020-03-30 | E-MTAB-8538 | biostudies-arrayexpress
Project description:Reduced PABPN1 levels cause aging-associated muscle wasting. PABPN1 is a multi-functional regulator of mRNA processing. To elucidate the molecular mechanisms causing PABPN1-mediated muscle wasting, we compared the transcriptome to the proteome in mouse muscles expressing shRNA to PABPN1 (shPab). We found greater variations in the proteome as compared to mRNA expression profiles. Protein accumulation in the shPab proteome was concomitant with reduced proteasomal activity. Notably, protein acetylation appeared to be enriched in shPab versus control proteomes (63%). An acetylome study in shPab muscles revealed prominent peptide deacetylation associated with elevated sirtuin-1 (SIRT1) deacetylase. We show that SIRT1 mRNA levels are controlled by PABPN1 via an alternative polyadenylation site utilization. SIRT1 inhibition reversed PABPN1 activity and muscle cell function. Moreover, deacetylation inhibition increased PABPN1 levels and reversed muscle wasting. We suggest that perturbation of a multifactorial regulatory loop involving PABPN1 and SIRT1 plays an imperative role in aging-associated muscle wasting.
2022-02-28 | PXD011534 | Pride
Project description:Poly(A) polymerase α (PAPα), as the specific mRNA polyadenylation enzyme in the cytoplasm of mammalian oocytes, is essential for oocytes to exclude the first polar body. However, PAPα knockout did not affect germinal vesicles breakdown (GVBD) of oocytes, and the mechanism needs to be further explored. In this study, we identified that PAPα work together with poly(A)-bound RNA binding protein PABPN1 to promote the rupture of germinal vesicles in mammalian oocytes. The protein level of Pabpn1 gradually increases with the meiotic maturation of oocytes. The oocytes specifically knocked out Pabpn1 at the primary follicle stage could develop into the fully grown (FGO) stage, but hardly could enter into the meiotic process. The activated form of CDK1 was injected into Pabpn1-null oocytes, the oocytes could enter into meiotic process. The translational activity of Pabpn1-null oocytes was significantly lower than that of wild-type oocytes during meiosis. In particular, the expression level of protein (BTG4 and CDC25), which were essential for the meiotic maturation of oocytes, were significantly decreased. Therefore, during the oocyte meiosis process, PABPN1 and PAPα jointly promote the oocyte to enter the meiosis process.
2022-08-23 | GSE184028 | GEO
Project description:Polyadenylation controls mRNA biogenesis, nuclear export, translation, and decay. These processes are interdependent and coordinately regulated by poly(A)-binding proteins (PABPs), yet how PABPs are themselves regulated is not fully understood. Here, we show that human PABPN1, the nuclear PABP, is phosphorylated by mitotic kinases at four specific sites during mitosis, a time when nucleoplasm and cytoplasm mix. Phospho-inhibitory mutations decreased human cell proliferation. We therefore employed long-read sequencing to determine how PABPN1 phospho-site mutants affected poly(A) tails lengths of individual mRNAs, and TimeLapse-seq to monitor mRNA synthesis and decay. Phospho-inhibitory PABPN1 mutants lengthened poly(A) tails on both spliced and unspliced transcripts. In contrast, expression of phospho-mimetic PABPN1 resulted in shorter poly(A) tails and reduced transcriptome stability, indicating reduced polyadenylation activity of PABPN1 and targeting of long-tailed transcripts for decay. Thus, PABPN1 phosphorylation confers transcriptome instability that is associated with resetting the gene expression program as cells passage through cell cycle.
2024-06-26 | GSE247007 | GEO
Project description:Identification of PABPN1 interacting proteins by proximity labeling with TurboID coupled with mass spectrometry.
2023-08-04 | PXD039864 | Pride
Project description:We present a genome-wide assessment of small open reading frames (smORF) translation by ribosomal profiling of polysomal fractions in Drosophila S2 cell. In this way, mRNAs bound by multiple ribosomes and hence actively translated can be isolated and distinguished from mRNAs bound by sporadic, putatively non-productive single ribosomes or ribosomal subunits. Ribosomal profiling of large and small polysomal fractions in Drosophila S2 cells to assess translation of smORFs
2014-09-11 | E-GEOD-60384 | biostudies-arrayexpress