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Sponsored by: Honors Program
Seminars: Tudor-SN-mediated MicroRNA Decay Promotes G1-to-S Phase Transition
Start Date/Time: 5/21/2018 4:00 PM
End Date/Time: 5/21/2018 5:00 PM
Location: Alumni Hall B
Description: 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 have 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. While TSN-mediated degradation of either protein-free or AGO2-loaded miRNAs does not require the ATP-dependent RNA helicase UPF1 in vitro, cellular TumiD requires UPF1. Results from experiments using AGO2-loaded miRNAs in duplex with target mRNAs indicate that UPF1 can dissociate miRNAs from their mRNA targets, making the miRNAs susceptible to TumiD.
Contact: Josephine Markiewicz
Phone: 263-3815
Email: Josephine.Markiewicz@nyumc.org
Speaker: Lynne Maquat, PhD
Speaker Institution: University of Rochester School of Medicine and Dentistry
Speaker Institution Location: Rochester, NY
Speaker Position: J.Lowell Orbison Endowed Chair and Professor of Biochemistry and Biophysics
Addtl. Info: Director, University of Rochester Center for RNA Biology: From Genome to Therapeutics. Chair, University of Rochester Graduate Women in Science
Seminar Host: Evgeny Nudler
Refreshments: No
Fee Required: No
Fee Amount:
 

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