Modulation of pre-mRNA structure by hnRNP proteins regulates alternative splicing of MALT1

Alisha N. Jones, Carina Gras, Isabel Meininger, Arie Geerlof, Melina Klostermann, Kathi Zarnack, K. Daniel, Michael Sattler

Research output: Contribution to journalArticlepeer-review


Alternative splicing plays key roles for cell type-specific regulation of protein function. It is controlled by cis-regulatory RNA elements that are recognized by RNA binding proteins (RBPs). The MALT1 paracaspase is a key factor of signaling pathways that mediate innate and adaptive immune responses. Alternative splicing of MALT1 is critical for controlling optimal T cell activation. We demonstrate that MALT1 splicing depends on RNA structural elements that sequester the splice sites of the alternatively spliced exon7. The RBPs hnRNP U and hnRNP L bind competitively to stem-loop RNA structures that involve the 5' and 3' splice sites flanking exon7. While hnRNP U stabilizes RNA stem-loop conformations that maintain exon7 skipping, hnRNP L disrupts these RNA elements to facilitate recruitment of the essential splicing factor U2AF2, thereby promoting exon7 inclusion. Our data represent a paradigm for the control of splice site selection by differential RBP binding and modulation of pre-mRNA structure.

Original languageEnglish (US)
Article numbereabp9153
JournalScience Advances
Issue number31
StatePublished - Aug 2022

ASJC Scopus subject areas

  • General


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