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

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

Author information

1
Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China.
2
Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
3
Institute of Tuberculosis Control, Key laboratory of Tropical Diseases Control, Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
4
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
5
Department of Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
6
Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA 92697, USA.

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.

PMID:
28911119
PMCID:
PMC5587809
DOI:
10.1093/nar/gkx651
[Indexed for MEDLINE]
Free PMC Article

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