PXD011617

PXD011617 is an original dataset announced via ProteomeXchange.

Title	PRMT1-mediated methylation of the Large Drosha Complex regulates microRNA biogenesis
Description	MicroRNA (miRNA) biogenesis is a tightly controlled multi-step process operated in the nucleus by the activity of the Large Drosha Complex (LDC). Through high resolution mass spectrometry (MS) analysis we discovered that the LDC is extensively methylated, with 82 distinct methylated sites associated to 16 out of 23 subunits of the LDC. The majority of these modifications occurs on arginine (R)- residues (61), leading to 86 methylation events, while 29 lysine (K)-methylation events occurs on 21 sites of the complex. Interestingly, the depletion and pharmacological inhibition of PRMT1 lead to a widespread alteration of the methylation state of the complex and induce global decrease of miRNA expression, as a consequence of the specific impairment of the pri-to-pre-miRNA processing step. In particular, we show that the reduced methylation of the ILF3 subunit of the complex is linked to its diminished binding to the target pri-miRNAs. Overall, our study uncovers a previously uncharacterized role of R-methylation in the regulation of the LDC activity in mammalian cells, thus effecting global miRNA levels.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:58:05.977.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Roberto Giambruno
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; N6,N6,N6-trimethyl-L-lysine; dimethylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-08 00:08:24	ID requested
1	2021-03-04 13:43:00	announced
⏵ 2	2024-10-22 04:58:06	announced	2024-10-22: Updated project metadata.

Spadotto V, Giambruno R, Massignani E, Mihailovich M, Maniaci M, Patuzzo F, Ghini F, Nicassio F, Bonaldi T, PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis. Nucleic Acids Res, 48(1):96-115(2020) [pubmed]

10.1093/nar/gkz1051;

curator keyword: Biomedical

submitter keyword: PRMT1,Large Drosha Complex, mass spectrometry, microRNA, protein methylation

Tiziana Bonaldi
contact affiliation	Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
contact email	tiziana.bonaldi@ieo.it
lab head
Roberto Giambruno
contact affiliation	IEO - European Institute of Oncology
contact email	roberto.giambruno@ieo.it
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/2019/10/PXD011617

PRIDE project URI

• PRIDE
  1. PXD011617
     1. Label: PRIDE project
     2. Name: PRMT1-mediated methylation of the Large Drosha Complex regulates microRNA biogenesis