Modulation of SF3B1 in the pre-mRNA spliceosome induces a RIG-I-dependent type I IFN response

Aaron Y. Chang, Yu Zhou, Sharanya Iyengar, Piotr W. Pobiarzyn, P. Ya. Tishchenko, Kesha M. Shah, Heather Wheeler, Yueming Wang, Paula M. Loria, Frank Loganzo,

Journal of Biological Chemistry · 2021 · 18 citations · 40 references

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Abstract

mutation, which leads to global aberrant splicing, had enhanced IFN-I response to canonical RIG-I agonism. Together, these results demonstrate that pharmacological modulation of SF3B1 in cancer cells can induce an enhanced IFN-I response dependent on RIG-I expression. The study suggests that spliceosome modulation may not only induce direct cancer cell cytotoxicity but also initiate an innate immune response via activation of RNA-sensing pathways.

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