Expression of transgenes enriched in rare codons is enhanced by the MAPK pathway

Abstract The ability to translate three nucleotide sequences, or codons, into amino acids to form proteins is conserved across all organisms. All but two amino acids have multiple codons, and the frequency that such synonymous codons occur in genomes ranges from rare to common. Transcripts enriched...

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Autores principales:	Jackson Peterson, Siqi Li, Erin Kaltenbrun, Ozgun Erdogan, Christopher M. Counter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/17e76f7a2dae49618c4d3c639c577d3c
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spelling	oai:doaj.org-article:17e76f7a2dae49618c4d3c639c577d3c2021-12-02T13:34:01ZExpression of transgenes enriched in rare codons is enhanced by the MAPK pathway10.1038/s41598-020-78453-52045-2322https://doaj.org/article/17e76f7a2dae49618c4d3c639c577d3c2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78453-5https://doaj.org/toc/2045-2322Abstract The ability to translate three nucleotide sequences, or codons, into amino acids to form proteins is conserved across all organisms. All but two amino acids have multiple codons, and the frequency that such synonymous codons occur in genomes ranges from rare to common. Transcripts enriched in rare codons are typically associated with poor translation, but in certain settings can be robustly expressed, suggestive of codon-dependent regulation. Given this, we screened a gain-of-function library for human genes that increase the expression of a GFPrare reporter encoded by rare codons. This screen identified multiple components of the mitogen activated protein kinase (MAPK) pathway enhancing GFPrare expression. This effect was reversed with inhibitors of this pathway and confirmed to be both codon-dependent and occur with ectopic transcripts naturally coded with rare codons. Finally, this effect was associated, at least in part, with enhanced translation. We thus identify a potential regulatory module that takes advantage of the redundancy in the genetic code to modulate protein expression.Jackson PetersonSiqi LiErin KaltenbrunOzgun ErdoganChristopher M. CounterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jackson Peterson Siqi Li Erin Kaltenbrun Ozgun Erdogan Christopher M. Counter Expression of transgenes enriched in rare codons is enhanced by the MAPK pathway
description	Abstract The ability to translate three nucleotide sequences, or codons, into amino acids to form proteins is conserved across all organisms. All but two amino acids have multiple codons, and the frequency that such synonymous codons occur in genomes ranges from rare to common. Transcripts enriched in rare codons are typically associated with poor translation, but in certain settings can be robustly expressed, suggestive of codon-dependent regulation. Given this, we screened a gain-of-function library for human genes that increase the expression of a GFPrare reporter encoded by rare codons. This screen identified multiple components of the mitogen activated protein kinase (MAPK) pathway enhancing GFPrare expression. This effect was reversed with inhibitors of this pathway and confirmed to be both codon-dependent and occur with ectopic transcripts naturally coded with rare codons. Finally, this effect was associated, at least in part, with enhanced translation. We thus identify a potential regulatory module that takes advantage of the redundancy in the genetic code to modulate protein expression.
format	article
author	Jackson Peterson Siqi Li Erin Kaltenbrun Ozgun Erdogan Christopher M. Counter
author_facet	Jackson Peterson Siqi Li Erin Kaltenbrun Ozgun Erdogan Christopher M. Counter
author_sort	Jackson Peterson
title	Expression of transgenes enriched in rare codons is enhanced by the MAPK pathway
title_short	Expression of transgenes enriched in rare codons is enhanced by the MAPK pathway
title_full	Expression of transgenes enriched in rare codons is enhanced by the MAPK pathway
title_fullStr	Expression of transgenes enriched in rare codons is enhanced by the MAPK pathway
title_full_unstemmed	Expression of transgenes enriched in rare codons is enhanced by the MAPK pathway
title_sort	expression of transgenes enriched in rare codons is enhanced by the mapk pathway
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/17e76f7a2dae49618c4d3c639c577d3c
work_keys_str_mv	AT jacksonpeterson expressionoftransgenesenrichedinrarecodonsisenhancedbythemapkpathway AT siqili expressionoftransgenesenrichedinrarecodonsisenhancedbythemapkpathway AT erinkaltenbrun expressionoftransgenesenrichedinrarecodonsisenhancedbythemapkpathway AT ozgunerdogan expressionoftransgenesenrichedinrarecodonsisenhancedbythemapkpathway AT christophermcounter expressionoftransgenesenrichedinrarecodonsisenhancedbythemapkpathway
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Expression of transgenes enriched in rare codons is enhanced by the MAPK pathway

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