Datasets

Title	Compromised nonsense-mediated RNA decay results in truncated RNA-binding protein production upon DUX4 expression
Organism
Number of Samples	12
Release Date	2021/06/23 00:00
Sequencing Types
Protocol Details

Title
Authors	Campbell AE,Dyle MC,Albanese R,Matheny T,Sudheendran K,Cortázar MA,Forman T,Fu R,Gillen AE,Caruthers MH,Floor SN,Calviello L,Jagannathan S
Journal	Cell reports
Publication Date	2023 Jun 27
Abstract	Nonsense-mediated RNA decay (NMD) degrades transcripts carrying premature termination codons. NMD is thought to prevent the synthesis of toxic truncated proteins. However, whether loss of NMD results in widespread production of truncated proteins is unclear. A human genetic disease, facioscapulohumeral muscular dystrophy (FSHD), features acute inhibition of NMD upon expression of the disease-causing transcription factor, DUX4. Using a cell-based model of FSHD, we show production of truncated proteins from physiological NMD targets and find that RNA-binding proteins are enriched for aberrant truncations. The NMD isoform of one RNA-binding protein, SRSF3, is translated to produce a stable truncated protein, which is detected in FSHD patient-derived myotubes. Ectopic expression of truncated SRSF3 confers toxicity, and its downregulation is cytoprotective. Our results delineate the genome-scale impact of NMD loss. This widespread production of potentially deleterious truncated proteins has implications for FSHD biology as well as other genetic diseases where NMD is therapeutically modulated. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
PMC	PMC10592454
PMID	37314931
DOI

Campbell et al. 2021 (PRJNA740301)