콘텐츠로 건너뛰기
Merck
  • PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis.

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

Nucleic acids research (2019-11-30)
Valeria Spadotto, Roberto Giambruno, Enrico Massignani, Marija Mihailovich, Marianna Maniaci, Francesca Patuzzo, Francesco Ghini, Francesco Nicassio, Tiziana Bonaldi
초록

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 23 sites of the complex. Interestingly, both depletion and pharmacological inhibition of the Type-I Protein Arginine Methyltransferases (PRMTs) lead to a widespread change in the methylation state of the complex and induce global decrease of miRNA expression, as a consequence of the impairment of the pri-to-pre-miRNA processing step. In particular, we show that the reduced methylation of the Microprocessor subunit ILF3 is linked to its diminished binding to the pri-miRNAs miR-15a/16, miR-17-92, miR-301a and miR-331. Our study uncovers a previously uncharacterized role of R-methylation in the regulation of miRNA biogenesis in mammalian cells.

MATERIALS
제품 번호
브랜드
제품 설명

Sigma-Aldrich
Anti-acetyl-Histone H4 Antibody, serum, Upstate®
Sigma-Aldrich
L-Methionine-(methyl-13C,d3), ≥99 atom % 13C, ≥99 atom % D, ≥99% (CP)
Sigma-Aldrich
L-Arginine monohydrochloride, not synthetic, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
L-Methionine, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 99.0-101.0%
Sigma-Aldrich
L-Lysine monohydrochloride, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%