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RNA Faculty Candidate Seminar: Dr. Alisha ‘Jonesy’ Jones, Institute of Structural Biology, Helmholtz Zentrum Munich
Monday, December 20, 2021 @ 4:00 pm - 5:00 pm
“Modulation of the MALT1 pre-mRNA structure by hnRNP proteins regulates T cell activation”
Dr. Alisha ‘Jonesy’ Jones
Institute of Structural Biology
Helmholtz Zentrum Munich
Co-Hosts: The Center for RNA Biomedicine, Department of Biological Chemistry, and the Program in Biophysics
In-person: Biomedical Science Research Buliding (BSRB), ABC Seminar rooms
Keywords: 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.