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

Chunliu Huang,Junjie Shi,Yibin Guo,Weijun Huang,Shanshan Huang,Siqi Ming,Xingui Wu,Rui Zhang,Junjun Ding,Wei Zhao,J. Jia,Xi Huang,A. Xiang,Yongsheng Shi,C. Yao

Published 2017 in Nucleic Acids Research

ABSTRACT

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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