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 language | English (US) |
|---|---|
| Pages (from-to) | 859-862 |
| Number of pages | 4 |
| Journal | Science |
| Volume | 356 |
| Issue number | 6340 |
| DOIs | |
| State | Published - May 26 2017 |
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All Science Journal Classification (ASJC) codes
- General
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Tudor-SN-mediated endonucleolytic decay of human cell microRNAs promotes G1/S phase transition. / Elbarbary, Reyad A.; Miyoshi, Keita; Myers, Jason R.; Du, Peicheng; Ashton, John M.; Tian, Bin; Maquat, Lynne E.
In: Science, Vol. 356, No. 6340, 26.05.2017, p. 859-862.Research output: Contribution to journal › Article
TY - JOUR
T1 - Tudor-SN-mediated endonucleolytic decay of human cell microRNAs promotes G1/S phase transition
AU - Elbarbary, Reyad A.
AU - Miyoshi, Keita
AU - Myers, Jason R.
AU - Du, Peicheng
AU - Ashton, John M.
AU - Tian, Bin
AU - Maquat, Lynne E.
PY - 2017/5/26
Y1 - 2017/5/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85019710474&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019710474&partnerID=8YFLogxK
U2 - https://doi.org/10.1126/science.aai9372
DO - https://doi.org/10.1126/science.aai9372
M3 - Article
C2 - 28546213
VL - 356
SP - 859
EP - 862
JO - Science
JF - Science
SN - 0036-8075
IS - 6340
ER -