Elongator and codon bias regulate protein levels in mammalian peripheral neurons

Joy Goffena, Frances Lefcort, Yongqing Zhang, Elin Lehrmann, Marta Chaverra, Jehremy Felig, Joseph Walters, Richard Buksch, Kevin G. Becker and Lynn George ()
Additional contact information
Joy Goffena: Montana State University Billings
Frances Lefcort: Montana State University
Yongqing Zhang: National Institutes of Health
Elin Lehrmann: National Institutes of Health
Marta Chaverra: Montana State University
Jehremy Felig: Montana State University Billings
Joseph Walters: Montana State University Billings
Richard Buksch: Montana State University Billings
Kevin G. Becker: National Institutes of Health
Lynn George: Montana State University Billings

Nature Communications, 2018, vol. 9, issue 1, 1-10

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

Date: 2018
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DOI: 10.1038/s41467-018-03221-z

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