Fundamental Themes in Neurosciences - Jernej Ule

Event Details:

Thursday, June 4, 2015
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Time
12:00pm to 1:00pm PDT
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Contacts
neuroscience@stanford.edu
Event Sponsor
Stanford Neurosciences Institute
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hiCLIP reveals the unforeseen prevalence of long-range secondary structures in the 3′ UTRs of mammalian mRNAs

 

 

Jermej Ule, Ph.D. Professor, Department of Molecular Neuroscience, UCL Institute of Neurology

 

Host: Ana Jovicic

Abstract

mRNA structure is important for post-transcriptional regulation, largely because it affects binding of trans-acting factors. However, little is known about the in vivo structure of full-length mRNAs. I will present hiCLIP, a high-throughput technique to identify RNA secondary structures interacting with RNA-binding proteins in vivo. By investigating RNA structures bound by Staufen 1 (STAU1), this technique uncovered a dominance of intra-molecular RNA duplexes, a depletion of duplexes from coding regions of highly translated mRNAs, an unforeseen prevalence of long-range duplexes in 3′ untranslated regions (UTRs), and a decreased incidence of SNPs in duplex-forming regions. Specifically, we identified a duplex spanning 858nts in the 3′ UTR of the X-box binding Protein 1 (XBP1) mRNA that regulates its cytoplasmic splicing and stability. I will discuss how hiCLIP can be used to discover novel, especially long-range, RNA duplexes bound by various types of RNA-binding proteins.