Nov 9, 2018

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

BioRxiv : the Preprint Server for Biology
Tiziana BonaldiFrancesco Nicassio

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 uncharacterised role of R-methylation in the regulation of the LDC activity in mammalian cells, thus affecting global miRNA levels.

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Mentioned in this Paper

Study
Protein Methylation
Primary MicroRNA
Regulation of Biological Process
LUM
Lysine acetyltransferase
Complex (molecular entity)
PRMT1
Methylate
RNASEN wt Allele

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