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

  • Author(s): Huang, Chunliu
  • Shi, Junjie
  • Guo, Yibin
  • Huang, Weijun
  • Huang, Shanshan
  • Ming, Siqi
  • Wu, Xingui
  • Zhang, Rui
  • Ding, Junjun
  • Zhao, Wei
  • Jia, Jie
  • Huang, Xi
  • Xiang, Andy Peng
  • Shi, Yongsheng
  • Yao, Chengguo
  • et al.
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.

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