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PXD031580

PXD031580 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe Heterochromatin protein 1 is a master regulator in RNA splicing precision deficient in ulcerative colitis
DescriptionDefects in RNA splicing have been linked to numerous human disorders, but remain poorly explored in inflammatory bowel disease (IBD). Here, we report that, in the gut epithelium of patients with ulcerative colitis (UC), the expression of the chromatin and alternative splicing regulator HP1g is strongly reduced. Accordingly, inactivation of the HP1g gene in the mouse gut triggered several IBD-like traits, including inflammation and dysbiosis. In parallel, we discovered that its loss of function broadly increased splicing noise, reducing requirement for canonical splicing consensus sequences, and favoring the usage of cryptic splice sites at numerous genes with key functions in gut biology. This notably resulted in the production of progerin, a noncanonical toxic splice variant of prelamin A mRNA, responsible for the Hutchinson Gilford Progeria Syndrome (HGPS) of premature aging. Likewise, production of progerin transcript was found to be a signature of colonic cells from UC patients. Thus, our study identifies HP1g as a regulator of RNA metabolism in vivo, providing a unique mechanism linking anti-inflammation and accuracy of RNA splicing in the gut epithelium. HP1 defect may confer a general disturbance in RNA splicing precision to scrutinize in IBD and more generally in accelerating aging diseases.
HostingRepositoryPRIDE
AnnounceDate2022-10-25
AnnouncementXMLSubmission_2022-10-25_08:58:37.651.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChiaraguerrera
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-02-10 14:56:45ID requested
12022-10-25 08:58:38announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: HP1
Contact List
ChiaraGuerrera
contact affiliationProteomics Platform Necker, Université de Paris - Structure Fédérative de Recherche Necker, INSERM US24/CNRS UMS3633, Paris, France.
contact emailchiara.guerrera@inserm.fr
lab head
Chiaraguerrera
contact affiliationNecker proteomics, INSERM
contact emailchiara.guerrera@inserm.fr
dataset submitter
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Dataset FTP location
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