PXD004865

PXD004865 is an original dataset announced via ProteomeXchange.

Title	Pabpn1-driven cytoskeletal rearrangement induces muscle wasting
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.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_10:05:01.841.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD004865
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Philip Charles
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Oxidation
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2016-08-18 03:37:44	ID requested
⏵ 1	2024-10-07 10:05:06	announced

10.1016/j.isci.2019.01.024;

Olie CS, Riaz M, Konietzny R, Charles PD, Pinto-Fernandez A, Kie, ł, basa SM, Aartsma-Rus A, Goeman JJ, Kessler BM, Raz V, Deacetylation Inhibition Reverses PABPN1-Dependent Muscle Wasting. iScience, 12():318-332(2019) [pubmed]

10.6019/PXD004865;

curator keyword: Biological, Biomedical

submitter keyword: Pfn1, Pabpn1,Mouse, Csrp3, Progenesis, LFQ, Murc

Vered Raz
contact affiliation	Department of Human Genetics Leiden University Medical Center Leiden The Netherlands
contact email	v.raz@lumc.nl
lab head
Philip Charles
contact affiliation	University of Oxford
contact email	philip.charles@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD004865
     1. Label: PRIDE project
     2. Name: Pabpn1-driven cytoskeletal rearrangement induces muscle wasting