title: Protein arginine methylation facilitates cotranscriptional recruitment of pre-mRNA splicing factors.
abstract: Cotranscriptional recruitment of pre-mRNA splicing factors to their genomic targets facilitates efficient and ordered assembly of a mature messenger ribonucleoprotein particle (mRNP). However, how the cotranscriptional recruitment of splicing factors is regulated remains largely unknown. Here, we demonstrate that protein arginine methylation plays a novel role in regulating this process in Saccharomyces cerevisiae. Our data show that Hmt1, the major type I arginine methyltransferase, methylates Snp1, a U1 small nuclear RNP (snRNP)-specific protein, and that the mammalian Snp1 homolog, U1-70K, is likewise arginine methylated. Genome-wide localization analysis reveals that the deletion of the HMT1 gene deregulates the recruitment of U1 snRNP and its associated components to intron-containing genes (ICGs). In the same context, splicing factors acting downstream of U1 snRNP addition bind to a reduced number of ICGs. Quantitative measurement of the abundance of spliced target transcripts shows that these changes in recruitment result in an increase in the splicing efficiency of developmentally regulated mRNAs. We also show that in the absence of either Hmt1 or of its catalytic activity, an association between Snp1 and the SR-like protein Npl3 is substantially increased. Together, these data support a model whereby arginine methylation modulates dynamic associations between SR-like protein and pre-mRNA splicing factor to promote target specificity in splicing.
authors.affiliation: Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Yin-Chu
authors.initials: YC
authors.lastname: Chen
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Milliman
authors.forename: Isabelle
authors.initials: I
authors.lastname: Goulet
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Côté
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Jackson
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Vollbracht
authors.forename: Michael C
authors.initials: MC
authors.lastname: Yu
mesh_terms: D001120:Arginine / Q000737:chemistry; D001665:Binding Sites / Q000235:genetics; D005800:Genes, Fungal; D007438:Introns; D008745:Methylation; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing / Q000235:genetics / Q000502:physiology*; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D012322:RNA Precursors; D012331:RNA, Fungal; D012097:Repressor Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; C096167:SNP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D001120:Arginine; C475182:HMT1 protein, S cerevisiae; D011484:Protein-Arginine N-Methyltransferases
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