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
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.