PXD011534-1

PXD011534 is an original dataset announced via ProteomeXchange.

Title	Deacetylation inhibition reverses PABPN1-dependent muscle wasting
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.
HostingRepository	PRIDE
AnnounceDate	2022-02-28
AnnouncementXML	Submission_2022-02-28_02:55:09.280.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD011534
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Cyriel Olie
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Deamidated; Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-10-30 09:16:50	ID requested
⏵ 1	2022-02-28 02:55:09	announced
2	2023-11-14 08:49:50	announced	2023-11-14: Updated project metadata.

10.1016/j.isci.2019.01.024;

submitter keyword: Muscle wasting, Deacetylation, SIRT1, mRNA processing, muscle proteome, muscle transcriptome

Benedikt M. Kessler
contact affiliation	Target Discovery Institute, Nuffield department of medicine, The university of Oxford
contact email	benedikt.kessler@ndm.ox.ac.uk
lab head
Cyriel Olie
contact affiliation	LUMC
contact email	c.s.olie@lumc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011534
     1. Label: PRIDE project
     2. Name: Deacetylation inhibition reverses PABPN1-dependent muscle wasting