Article
Nonsense-Mediated RNA Decay Is a Targetable Vulnerability in Splicing Factor Mutant Myeloid Neoplasms by Enhancing R-Loop Accumulation and DNA Damage.
Cancer research - 15 Jul 2026
Pastrana Claudia C, Nonavinkere Srivatsan Sridhar, Alberti Michael O, Hossan Tareq, Ahmed Tanzir, Shao Jin, Chavez Monique, Grieb Sarah, Padro Julia I, Paul Dhanya M, George Daniel R, Patil Ashwini, Rai Sumit, Graubert Timothy A, Bailis Julie M, You Zhongsheng, Walter Matthew J
Abstract excerpt
Mutant spliceosome proteins (e.g., U2AF1S34F, SF3B1K700E, or SRSF2P95H) alter RNA splicing in myeloid neoplasms, leading to increased production of nonsense transcripts. Inhibiting the nonsense-mediated RNA decay (NMD) pathway, which is responsible for the degradation of nonsense transcripts, preferentially kills cells expressing mutant spliceosome proteins in vitro. In this study, we used an inhibitor of the...
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