PXD013856

PXD013856 is an original dataset announced via ProteomeXchange.

Title	Stabilizing Heterochromatin by DGCR8 Alleviates Senescence and Osteoarthritis
Description	DiGeorge syndrome critical region 8 (DGCR8) is a critical component of the canonical microprocessor complex for microRNA biogenesis. However, the non-canonical functions of DGCR8 have not been studied. Here, we demonstrate that DGCR8 plays an important role in maintaining heterochromatin organization and attenuating aging. An N-terminal-truncated version of DGCR8 (DR8dex2) accelerated senescence in human mesenchymal stem cells (hMSCs) independent of its miRNA-processing activity, which is mediated by its C-terminal domains. Further studies revealed that DGCR8 maintained heterochromatin organization by interacting with the nuclear envelope protein Lamin B1, and heterochromatin-associated proteins, KAP1 and HP1 Overexpression of any of these proteins, including DGCR8, reversed premature senescent phenotypes in DR8dex2 hMSCs. Finally, DGCR8 was downregulated in pathologically and naturally aged hMSCs, whereas DGCR8 overexpression alleviated hMSC aging and osteoarthritis in mice. Taken together, these analyses uncovered a novel, miRNA processing-independent role for DGCR8 in maintaining heterochromatin organization and attenuating senescence. DGCR8 may therefore represent a new therapeutic target for alleviating human aging-related disorders.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:54:01.174.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zunpeng Liu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-15 03:24:00	ID requested
1	2019-05-28 05:58:34	announced
2	2019-08-01 04:39:33	announced	Updated publication reference for PubMed record(s): 31350386.
⏵ 3	2024-10-22 04:54:02	announced	2024-10-22: Updated project metadata.

10.1038/s41467-019-10831-8;

Deng L, Ren R, Liu Z, Song M, Li J, Wu Z, Ren X, Fu L, Li W, Zhang W, Guillen P, Izpisua Belmonte JC, Chan P, Qu J, Liu GH, Stabilizing heterochromatin by DGCR8 alleviates senescence and osteoarthritis. Nat Commun, 10(1):3329(2019) [pubmed]

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: DGCR8, heterochromatin, aging

Guang-Hui Liu
contact affiliation	National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
contact email	zunpengliu@163.com
lab head
Zunpeng Liu
contact affiliation	IBP, CAS
contact email	zunpengliu@163.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013856

PRIDE project URI

• PRIDE
  1. PXD013856
     1. Label: PRIDE project
     2. Name: Stabilizing Heterochromatin by DGCR8 Alleviates Senescence and Osteoarthritis