Proteomics

Dataset Information

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PRMT1-mediated methylation of the Large Drosha Complex regulates microRNA biogenesis


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Hela Cell

DISEASE(S): Cervix Carcinoma

SUBMITTER: Roberto Giambruno  

LAB HEAD: Tiziana Bonaldi

PROVIDER: PXD011617 | Pride | 2019-10-23

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
F130509_VS_IP_DDX5_01.raw Raw
F130509_VS_IP_DDX5_02.raw Raw
F130509_VS_IP_DDX5_03.raw Raw
F130509_VS_IP_DDX5_04.raw Raw
F130509_VS_IP_DDX5_05.raw Raw
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Publications

PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis.

Spadotto Valeria V   Giambruno Roberto R   Massignani Enrico E   Mihailovich Marija M   Maniaci Marianna M   Patuzzo Francesca F   Ghini Francesco F   Nicassio Francesco F   Bonaldi Tiziana T  

Nucleic acids research 20200101 1


MicroRNA (miRNA) biogenesis is a tightly controlled multi-step process operated in the nucleus by the activity of the Microprocessor and its associated proteins. Through high resolution mass spectrometry (MS)- proteomics we discovered that this complex is extensively methylated, with 84 methylated sites associated to 19 out of its 24 subunits. The majority of the modifications occurs on arginine (R) residues (61), leading to 81 methylation events, while 30 lysine (K)-methylation events occurs on  ...[more]

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