Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum

Abstract Plasmodium falciparum genome has 81% A+T content. This nucleotide bias leads to extreme codon usage bias and culminates in frequent insertion of asparagine homorepeats in the proteome. Using recodonized GFP sequences, we show that codons decoded via G:U wobble pairing are suboptimal codons...

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Autores principales:	Sherwin Chan, Jun-Hong Ch’ng, Mats Wahlgren, Jessada Thutkawkorapin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a00b8d1b6c5a4836ba5159d5faf03e89
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spelling	oai:doaj.org-article:a00b8d1b6c5a4836ba5159d5faf03e892021-12-02T12:30:53ZFrequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum10.1038/s41598-017-00801-92045-2322https://doaj.org/article/a00b8d1b6c5a4836ba5159d5faf03e892017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00801-9https://doaj.org/toc/2045-2322Abstract Plasmodium falciparum genome has 81% A+T content. This nucleotide bias leads to extreme codon usage bias and culminates in frequent insertion of asparagine homorepeats in the proteome. Using recodonized GFP sequences, we show that codons decoded via G:U wobble pairing are suboptimal codons that are negatively associated to protein translation efficiency. Despite this, one third of all codons in the genome are GU wobble codons, suggesting that codon usage in P. falciparum has not been driven to maximize translation efficiency, but may have evolved as translational regulatory mechanism. Particularly, asparagine homorepeats are generally encoded by locally clustered GU wobble AAT codons, we demonstrated that this GU wobble-rich codon context is the determining factor that causes reduction of protein level. Moreover, insertion of clustered AAT codons also causes destabilization of the transcripts. Interestingly, more frequent asparagine homorepeats insertion is seen in single-exon genes, suggesting transcripts of these genes may have been programmed for rapid mRNA decay to compensate for the inefficiency of mRNA surveillance regulation on intronless genes. To our knowledge, this is the first study that addresses P. falciparum codon usage in vitro and provides new insights on translational regulation and genome evolution of this parasite.Sherwin ChanJun-Hong Ch’ngMats WahlgrenJessada ThutkawkorapinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sherwin Chan Jun-Hong Ch’ng Mats Wahlgren Jessada Thutkawkorapin Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum
description	Abstract Plasmodium falciparum genome has 81% A+T content. This nucleotide bias leads to extreme codon usage bias and culminates in frequent insertion of asparagine homorepeats in the proteome. Using recodonized GFP sequences, we show that codons decoded via G:U wobble pairing are suboptimal codons that are negatively associated to protein translation efficiency. Despite this, one third of all codons in the genome are GU wobble codons, suggesting that codon usage in P. falciparum has not been driven to maximize translation efficiency, but may have evolved as translational regulatory mechanism. Particularly, asparagine homorepeats are generally encoded by locally clustered GU wobble AAT codons, we demonstrated that this GU wobble-rich codon context is the determining factor that causes reduction of protein level. Moreover, insertion of clustered AAT codons also causes destabilization of the transcripts. Interestingly, more frequent asparagine homorepeats insertion is seen in single-exon genes, suggesting transcripts of these genes may have been programmed for rapid mRNA decay to compensate for the inefficiency of mRNA surveillance regulation on intronless genes. To our knowledge, this is the first study that addresses P. falciparum codon usage in vitro and provides new insights on translational regulation and genome evolution of this parasite.
format	article
author	Sherwin Chan Jun-Hong Ch’ng Mats Wahlgren Jessada Thutkawkorapin
author_facet	Sherwin Chan Jun-Hong Ch’ng Mats Wahlgren Jessada Thutkawkorapin
author_sort	Sherwin Chan
title	Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum
title_short	Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum
title_full	Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum
title_fullStr	Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum
title_full_unstemmed	Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum
title_sort	frequent gu wobble pairings reduce translation efficiency in plasmodium falciparum
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a00b8d1b6c5a4836ba5159d5faf03e89
work_keys_str_mv	AT sherwinchan frequentguwobblepairingsreducetranslationefficiencyinplasmodiumfalciparum AT junhongchng frequentguwobblepairingsreducetranslationefficiencyinplasmodiumfalciparum AT matswahlgren frequentguwobblepairingsreducetranslationefficiencyinplasmodiumfalciparum AT jessadathutkawkorapin frequentguwobblepairingsreducetranslationefficiencyinplasmodiumfalciparum
_version_	1718394295967285248

Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum

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