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Presented By: Center for RNA Biomedicine

RNA Faculty Candidate Seminar

Dr. Alisha 'Jonesy' Jones, Institute of Structural Biology, Helmholtz Zentrum Munich

Alisha (Jonesy) Jones, Ph.D. Alisha (Jonesy) Jones, Ph.D.
Alisha (Jonesy) Jones, Ph.D.
In-person/Hybrid seminar co-hosted by the Center for RNA Biomedicine, the Department of Biological Chemistry and the Department of Biophysics

Talk title: “Modulation of the MALT1 pre-mRNA structure by hnRNP proteins regulates T cell activation”

Key words: pre-mRNA, hnRNP, NMR, SHAPE, structure
Abstract: Alternative splicing is controlled by differential binding of trans-acting RNA binding proteins (RBPs) to cis-regulatory pre-mRNA elements. How pre-mRNA secondary structure affects recognition by RBPs and determines alternative exon usage is poorly understood. The MALT1 paracaspase is a key component of signaling pathways that mediate innate and adaptive immune responses. Alternative splicing of MALT1 exon7 is critical for controlling optimal T cell activation. Here, we demonstrate that MALT1 pre-mRNA splicing depends on RNA structural elements that shield the splice sites of the alternatively spliced exon7. The RBPs hnRNP U and hnRNP L bind comparably and competitively to identical stem-loop RNA structures flanking the 5’ and 3’ splice sites of MALT1 exon7. While hnRNP U stabilizes RNA stem-loop conformations that maintain exon7 skipping, hnRNP L destabilizes these RNA elements to facilitate recruitment of the essential splicing factor U2AF2 to promote exon7 inclusion. This work represents a paradigm for the control of splice site selection by differential RBP binding and modulation of pre-mRNA structure.

If you are having trouble registering, please contact Martina Jerant at mjerant@umich.edu

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