PXD029228

PXD029228 is an original dataset announced via ProteomeXchange.

Title	Dysregulated RNA polyadenylation contributes to metabolic impairment in non-alcoholic fatty liver disease
Description	Pre-mRNA processing is an essential mechanism for the generation of mature mRNA and the regulation of gene expression in eukaryotic cells. While defects in pre-mRNA processing have been implicated in a number of diseases their involvement in metabolic pathologies is still unclear. Here we show that both alternative splicing and alternative polyadenylation, two major steps in pre-mRNA processing, are significantly altered in non-alcoholic fatty liver disease (NAFLD). Moreover, we find that Serine and Arginine Rich Splicing Factor 10 (SRSF10) binding is enriched adjacent to consensus polyadenylation motifs and its expression is significantly decreased in NAFLD, suggesting a role mediating pre-mRNA dysregulation in this condition. Consistently, inactivation of SRSF10 in mouse and human hepatocytes in vitro, and in mouse liver in vivo, was found to dysregulate polyadenylation of key metabolic genes such as peroxisome proliferator activated receptor alpha (PPARA) and exacerbate diet-induced metabolic dysfunction. Collectively our work implicates dysregulated pre-mRNA polyadenylation in obesity-induced liver disease and uncovers a novel role for SRSF10 in this process.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-20_23:56:35.475.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex Montoya
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue; acetylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-20 03:05:03	ID requested
⏵ 1	2022-05-20 23:56:36	announced

Jobbins AM, Haberman N, Artigas N, Amourda C, Paterson HAB, Yu S, Blackford SJI, Montoya A, Dore M, Wang YF, Sardini A, Cebola I, Zuber J, Rashid ST, Lenhard B, Vernia S, Dysregulated RNA polyadenylation contributes to metabolic impairment in non-alcoholic fatty liver disease. Nucleic Acids Res, 50(6):3379-3393(2022) [pubmed]

submitter keyword: SR protein, Splicing factor, RNA polyadenylation, RNA alternative splicing, NAFLD, obesity, liver.

Dr Pavel Shliaha
contact affiliation	Head of Proteomics and Metabolomics Facility
contact email	p.shliaha@lms.mrc.ac.uk
lab head
Alex Montoya
contact affiliation	Medical Research Council - London Institute of Medical Sciences
contact email	alex.montoya@lms.mrc.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029228
     1. Label: PRIDE project
     2. Name: Dysregulated RNA polyadenylation contributes to metabolic impairment in non-alcoholic fatty liver disease