biostudies-literatureBelleville AEFred Hutchinson Cancer Research CenterPaul G. Allen Frontiers GroupNHLBI NIH HHSNational Heart, Lung, and Blood InstituteMark Foundation For Cancer ResearchNational Cancer InstituteNCI NIH HHSMcIlwain Family Endowed ChairNIH HHSLeukemia and Lymphoma Societye1011363https://www.ebi.ac.uk/biostudies/studies/S-EPMC11357089biostudies-literatureUnknown20(8)Many of the most highly conserved elements in the human genome are "poison exons," alternatively spliced exons that contain premature termination codons and permit post-transcriptional regulation of mRNA abundance through induction of nonsense-mediated mRNA decay (NMD). Poison exons are widely assumed to be highly conserved due to their presumed importance for organismal fitness, but this functional importance has never been tested in the context of a whole organism. Here, we report that a poison exon in Smndc1 is conserved across mammals and plants and plays a molecular autoregulatory function in both kingdoms. We generated mouse and A. thaliana models lacking this poison exon to find its loss leads to deregulation of SMNDC1 protein levels, pervasive alterations in mRNA processing, and orPLoS geneticsAn autoregulatory poison exon in Smndc1 is conserved across kingdoms and influences organism growth.PMC11357089R01 HL151651P30 CA015704S10 OD028685R01 HL1282398023-20R01 CA2511381344-18Queitsch CTonnies JGabel AMBorrero Rossi ABradley RKThomas JDSingh PBelleville AEfalseAn autoregulatory poison exon in Smndc1 is conserved across kingdoms and influences organism growth.Many of the most highly conserved elements in the human genome are "poison exons," alternatively spliced exons that contain premature termination codons and permit post-transcriptional regulation of mRNA abundance through induction of nonsense-mediated mRNA decay (NMD). Poison exons are widely assumed to be highly conserved due to their presumed importance for organismal fitness, but this functional importance has never been tested in the context of a whole organism. Here, we report that a poison exon in Smndc1 is conserved across mammals and plants and plays a molecular autoregulatory function in both kingdoms. We generated mouse and A. thaliana models lacking this poison exon to find its loss leads to deregulation of SMNDC1 protein levels, pervasive alterations in mRNA processing, and or2024-01-01T00:00:00Z2024 Aug2025-04-26T21:24:34.045Z2025-04-06T16:47:39.436ZS-EPMC113570893915099110.1371/journal.pgen.1011363