Pervasive changes of mRNA splicing in upf1-deficient zebrafish identify rpl10a as a regulator of T cell development Divine-Fondzenyuy Lawir, Katarzyna Sikora, Connor P. O’Meara, Michael Schorpp, Thomas Boehm 

Erscheinungsform: einbändiges Werk
Autor/Urheber:
  • Lawir, Divine Fondzenyuy
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Umfang: 1 Online-Ressource (10 Seiten) Diagramme
Identifikatoren/​Sonstige Nummern: 1758958782 [PPN]
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  • Abstract: The transcriptome of eukaryotic cells is constantly monitored for errors to avoid the production of undesired protein variants. The evolutionarily conserved nonsense-mediated mRNA decay (NMD) pathway degrades aberrant mRNAs, but also functions in the regulation of transcript abundance in response to changed physiological states. Here, we describe a zebrafish mutant of upf1, encoding the central component of the NMD machinery. Fish homozygous for the upf1t20450 allele (Y163X) survive until day 10 after fertilization, presenting with impaired T cell development as one of the most conspicuous features of the mutant phenotype. Analysis of differentially expressed genes identified dysregulation of the pre-mRNA splicing pathway, accompanied by perturbed autoregulation of canonical splicing activators (SRSF) and repressors (HNRNP). In upf1-deficient mutants, NMD-susceptible transcripts of ribosomal proteins that are known for their role as noncanonical splicing regulators were greatly increased, most notably, rpl10a. When the levels of NMD-susceptible rpl10a transcripts were artificially increased in zebrafish larvae, T cell development was significantly impaired, suggesting that perturbed autoregulation of rpl10a splicing contributes to failing T cell development in upf1 deficiency. Our results identify an extraribosomal tissue-specific function to rpl10a in the immune system, and thus exemplify the advantages of the zebrafish model to study the effects of upf1-deficiency in the context of a vertebrate organism
URL: https://nbn-resolving.de/urn:nbn:de:bsz:25-freidok-1757875
Weiter im Partnersystem: https://swb.bsz-bw.de/DB=2.1/PPNSET?PPN=1758958782
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