Proteomics

Dataset Information

0

Pabpn1-driven cytoskeletal rearrangement induces muscle wasting

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Tibialis Anterior

SUBMITTER: Philip Charles  

LAB HEAD: Vered Raz

PROVIDER: PXD004865 | Pride | 2020-07-06

REPOSITORIES: Pride

Json Xml

Dataset's files

Source:
Action DRS
CyrielOlie.mzid.gz Mzid
CyrielOlie.pride.mztab.gz Mztab
HF0049a_COlie_20151007_LR_scr_11.raw Raw
HF0049a_COlie_20151007_LR_shRNA_12.raw Raw
HF0049a_COlie_20151007_L_scr_5.raw Raw
Items per page:
1 - 5 of 20
altmetric image

Publications

Reduced poly(A)-binding protein nuclear 1 (PABPN1) levels cause aging-associated muscle wasting. PABPN1 is a multifunctional regulator of mRNA processing. To elucidate the molecular mechanisms causing PABPN1-mediated muscle wasting, we compared the transcriptome with the proteome in mouse muscles expressing short hairpin RNA to PABPN1 (shPab). We found greater variations in the proteome than in mRNA expression profiles. Protein accumulation in the shPab proteome was concomitant with reduced prot  ...[more]

Similar Datasets

Proteomics Deacetylation inhibition reverses PABPN1-dependent muscle wasting
2022-02-28 | PXD011534 | Pride
Transcriptomics Thorax transcriptome from control and PABPN1-17ala-expressing flies
2014-12-12 | GSE64094 | GEO
Transcriptomics Transcriptome of tibialis anterior muscle RNA samples from control and OPMD A17.1 mouse treated or not with a gene therapy approach
2017-06-12 | GSE89996 | GEO
Transcriptomics Regulation of alternative cleavage and polyadenylation by 3’ end processing and splicing factors
2015-04-01 | E-GEOD-62001 | biostudies-arrayexpress
Transcriptomics Role of the Cytoskeleton in muscle transcriptional response to altered use
2012-10-06 | E-GEOD-41363 | biostudies-arrayexpress
Transcriptomics Farnesol prevents aging-related muscle weakness in mice through enhanced farnesylation of Parkin-interacting substrate
2023-08-12 | GSE240281 | GEO
Proteomics Deep proteome of aging skeletal muscles reveals Smoc2 as a modulator of satellite cell regenerative capacity
2021-11-25 | PXD015616 | Pride
Proteomics Deep proteome of aging skeletal muscles reveals Smoc2 as a modulator of satellite cell regenerative capacity
2021-11-25 | PXD015728 | Pride
Transcriptomics Regulation of alternative cleavage and polyadenylation by 3’ end processing and splicing factors
2015-04-01 | GSE62001 | GEO
Transcriptomics Mechanical regulation of the glucocorticoid-sensitive transcriptome in young and aged skeletal muscle
2024-10-28 | GSE269698 | GEO