Understanding the RNA-dependent regulation of NFKBIZ by Regnase-1 and the development of RNA imaging and pulldown tools

(This conference will take place in English.)

Peter Unrau, PhD
Professor
Dept of Molecular Biology and Biochemistry,
Simon Fraser University
 

This conference is hosted by Tarik Möröy and will be held in person in the IRCM André-Barbeau Room.

About this conference

A specific class of mutations in the 3’ UTR of NFKBIZ, known to drive B-cell lymphoma formation, disrupt a conserved RNA motif that we have recently characterized and shown to be precisely cleaved by Regnase-1. Alterations to this RNA structure—whether introduced experimentally or via known disease-associated mutations—significantly impair Regnase-1-mediated cleavage in vitro. The disruptions observed in vitro are closely correlated with increased luciferase reporter protein expression in human cell culture. Notably in this respect, we find compelling evidence that that after being cleaved the endogenous NFKBIZ RNA fragment undergoes extensive 3’ uridylation—a modification known to dramatically accelerate RNA decay in other cellular contexts and that suggests a cellular mechanism that directly links Regnase-1 cleavage rate to the lifetime of the NFKBIZ open reading frame and hence protein abundances. I will also present my laboratories development of RNA Mango: a fluorogenic RNA imaging and pulldown research tool designed to investigate native RNA molecules and RNA–protein complexes in living cells.

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