Elongator and codon bias regulate protein levels in mammalian peripheral neurons

• DOI: 10.1038/s41467-018-03221-z
• Publication Date: 2018-02-23T10:43:04Z
• Authors: Joy Goffena; Frances Lefcort; Yongqing Zhang; Elin Lehrmann; Marta Chaverra; Jehremy Felig; Joseph Walters; Richard Buksch; Kevin G. Becker; Lynn George
• Keywords: Loss function; Stop codon; Proteome

Familial dysautonomia (FD) results from mutation in IKBKAP/ELP1, a gene encoding the scaffolding protein for Elongator complex. This highly conserved complex is required translation of codon-biased genes lower organisms. Here we investigate whether serves similar function mammalian peripheral neurons, population devastated FD. Using eGFP sensors, and multiplexing codon usage with transcriptome proteome analyses over 6,000 genes, identify two categories as well specific identities that depend on normal expression. Moreover, show multiple DNA damage repair pathway are codon-biased, loss, their misregulation correlated elevated levels damage. These findings link Elongator's both developmental neurodegenerative phenotypes FD, also clarify increased risk cancer associated disease.