Alternative splicing of MALT1 controls signalling and activation of CD4(+) T cells

Alternative splicing of MALT1 controls signalling and activation of CD4(+) T cells
Meininger I, Griesbach RA, Hu D, Gehring T, Seeholzer T, Bertossi A, Kranich J, Oeckinghaus A, Eitelhuber AC, Greczmiel U, Gewies A, Schmidt-Supprian M, Ruland J, Brocker T, Heissmeyer V, Heyd F, Krappmann D
Nat Commun. 2016 Apr 12;7:11292. doi: 10.1038/ncomms11292.

MALT1 channels proximal T-cell receptor (TCR) signalling to downstream signalling pathways. With MALT1A and MALT1B two conserved splice variants exist and we demonstrate here that MALT1 alternative splicing supports optimal T-cell activation. Inclusion of exon7 in MALT1A facilitates the recruitment of TRAF6, which augments MALT1 scaffolding function, but not protease activity. Naive CD4(+) T cells express almost exclusively MALT1B and MALT1A expression is induced by TCR stimulation. We identify hnRNP U as a suppressor of exon7 inclusion. Whereas selective depletion of MALT1A impairs T-cell signalling and activation, downregulation of hnRNP U enhances MALT1A expression and T-cell activation. Thus, TCR-induced alternative splicing augments MALT1 scaffolding to enhance downstream signalling and to promote optimal T-cell activation.