Tudor-SN-mediated endonucleolytic decay of human cell microRNAs promotes G1/S phase transition

Reyad A. Elbarbary, Keita Miyoshi, Jason R. Myers, Peicheng Du, John M. Ashton, Bin Tian, Lynne E. Maquat

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression. The pathways that mediate mature miRNA decay are less well understood than those that mediate miRNA biogenesis.We found that functional miRNAs are degraded in human cells by the endonuclease Tudor-SN (TSN). In vitro, recombinant TSN initiated the decay of both protein-free and Argonaute 2-loaded miRNAs via endonucleolytic cleavage at CA and UA dinucleotides, preferentially at scissile bonds located more than five nucleotides away from miRNA ends. Cellular targets of TSN-mediated decay defined using microRNA sequencing followed this rule. Inhibiting TSN-mediated miRNA decay by CRISPR-Cas9 knockout of TSN inhibited cell cycle progression by up-regulating a cohort of miRNAs that down-regulates mRNAs that encode proteins critical for the G1-to-S phase transition. Our study indicates that targeting TSN nuclease activity could inhibit pathological cell proliferation.

Original languageEnglish (US)
Pages (from-to)859-862
Number of pages4
JournalScience
Volume356
Issue number6340
DOIs
StatePublished - May 26 2017

All Science Journal Classification (ASJC) codes

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    Elbarbary, R. A., Miyoshi, K., Myers, J. R., Du, P., Ashton, J. M., Tian, B., & Maquat, L. E. (2017). Tudor-SN-mediated endonucleolytic decay of human cell microRNAs promotes G1/S phase transition. Science, 356(6340), 859-862. https://doi.org/10.1126/science.aai9372