Zebrafish rbm8a and magoh mutants reveal EJC developmental functions and new 3′UTR intron-containing NMD targets

• DOI: 10.1371/journal.pgen.1008830
• Publication Date: 2020-06-05T17:54:07Z
• Authors: Pooja Gangras; Thomas L. Gallagher; Michael A. Parthun; Zhongxia Yi; Robert D. Patton; Kiel T. Tietz; Natalie C. Deans; Ralf Bundschuh; Sharon L. Amacher; Guramrit Singh
• Keywords: Nonsense-Mediated Decay

Many post-transcriptional mechanisms operate via mRNA 3′UTRs to regulate protein expression, and such controls are crucial for development. We show that homozygous mutations in two zebrafish exon junction complex (EJC) core genes rbm8a magoh leads muscle disorganization, neural cell death, motor neuron outgrowth defects, as well dysregulation of mRNAs subjected nonsense-mediated decay (NMD) due translation termination ≥ 50 nts upstream the last exon-exon junction. Intriguingly, we find EJC-dependent NMD also regulates a subset transcripts contain 3′UTR introns (3′UI) < downstream stop codon. Some containing codon-proximal 3′UI NMD-sensitive cultured human cells mouse embryonic stem cells. identify 167 conserved proximal zebrafish, humans. foxo3b is one 3′UI-containing gene upregulated EJC mutant embryos, at both levels, loss function embryos significantly rescues axon growth defects. These data consistent with regulating control expression during Our work shows critical normal development suggests 3′UIs may serve regulatory vertebrates.