A snoRNA modulates mRNA 3' end processing and regulates the expression of a subset of mRNAs

Nucleic Acids Res. 2017 Sep 6;45(15):8647-8660. doi: 10.1093/nar/gkx651.

Abstract

mRNA 3' end processing is an essential step in gene expression. It is well established that canonical eukaryotic pre-mRNA 3' processing is carried out within a macromolecular machinery consisting of dozens of trans-acting proteins. However, it is unknown whether RNAs play any role in this process. Unexpectedly, we found that a subset of small nucleolar RNAs (snoRNAs) are associated with the mammalian mRNA 3' processing complex. These snoRNAs primarily interact with Fip1, a component of cleavage and polyadenylation specificity factor (CPSF). We have functionally characterized one of these snoRNAs and our results demonstrated that the U/A-rich SNORD50A inhibits mRNA 3' processing by blocking the Fip1-poly(A) site (PAS) interaction. Consistently, SNORD50A depletion altered the Fip1-RNA interaction landscape and changed the alternative polyadenylation (APA) profiles and/or transcript levels of a subset of genes. Taken together, our data revealed a novel function for snoRNAs and provided the first evidence that non-coding RNAs may play an important role in regulating mRNA 3' processing.

MeSH terms

  • Cleavage And Polyadenylation Specificity Factor / metabolism
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Monomeric GTP-Binding Proteins / metabolism
  • Poly A / metabolism
  • Protein Binding
  • RNA 3' End Processing / genetics*
  • RNA, Messenger / metabolism*
  • RNA, Small Nucleolar / metabolism
  • RNA, Small Nucleolar / physiology*
  • mRNA Cleavage and Polyadenylation Factors / metabolism

Substances

  • Cleavage And Polyadenylation Specificity Factor
  • RNA, Messenger
  • RNA, Small Nucleolar
  • mRNA Cleavage and Polyadenylation Factors
  • Poly A
  • RRAGA protein, human
  • Monomeric GTP-Binding Proteins