Coding-Sequence Determinants of Gene Expression in Escherichia coli

被引：1092

作者：

Kudla, Grzegorz ^{[1
,2
]}

Murray, Andrew W. ^{[3
]}

Tollervey, David ^{[4
,5
]}

Plotkin, Joshua B. ^{[1
,2
]}

机构：

[1] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA

[2] Univ Penn, Program Appl Math & Computat Sci, Philadelphia, PA 19104 USA

[3] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[4] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland

[5] Univ Edinburgh, Ctr Syst Biol, Edinburgh EH9 3JR, Midlothian, Scotland

来源：

SCIENCE | 2009年 / 324卷 / 5924期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

SYNONYMOUS CODON USAGE; RNA SECONDARY STRUCTURE; MESSENGER-RNA; TRANSLATION INITIATION; PROTEIN EXPRESSION; BIAS; DOWNSTREAM; MUTATIONS; STABILITY; SELECTION;

D O I：

10.1126/science.1170160

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Synonymous mutations do not alter the encoded protein, but they can influence gene expression. To investigate how, we engineered a synthetic library of 154 genes that varied randomly at synonymous sites, but all encoded the same green fluorescent protein (GFP). When expressed in Escherichia coli, GFP protein levels varied 250-fold across the library. GFP messenger RNA (mRNA) levels, mRNA degradation patterns, and bacterial growth rates also varied, but codon bias did not correlate with gene expression. Rather, the stability of mRNA folding near the ribosomal binding site explained more than half the variation in protein levels. In our analysis, mRNA folding and associated rates of translation initiation play a predominant role in shaping expression levels of individual genes, whereas codon bias influences global translation efficiency and cellular fitness.

引用

页码：255 / 258

页数：4

共 28 条

[1]

AKASHI H, 1994, GENETICS, V136, P927

[2] CODON PREFERENCES IN FREE-LIVING MICROORGANISMS [J].

ANDERSSON, SGE ;

KURLAND, CG .

MICROBIOLOGICAL REVIEWS, 1990, 54 (02) :198-210

[3] Codon pairs in the genome of Escherichia coli [J].

Boycheva, S ;

Chkodrov, G ;

Ivanov, I .

BIOINFORMATICS, 2003, 19 (08) :987-998

[4] Virus attenuation by genome-scale changes in codon pair bias [J].

Coleman, J. Robert ;

Papamichail, Dimitris ;

Skiena, Steven ;

Futcher, Bruce ;

Wimmer, Eckard ;

Mueller, Steffen .

SCIENCE, 2008, 320 (5884) :1784-1787

[5] A codon window in mRNA downstream of the initiation codon where NGG codons give strongly reduced gene expression in Escherichia coli [J].

de Valdivia, EIG ;

Isaksson, LA .

NUCLEIC ACIDS RESEARCH, 2004, 32 (17) :5198-5205

[6] SECONDARY STRUCTURE OF THE RIBOSOME BINDING-SITE DETERMINES TRANSLATIONAL EFFICIENCY - A QUANTITATIVE-ANALYSIS [J].

DESMIT, MH ;

VANDUIN, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (19) :7668-7672

[7] Why highly expressed proteins evolve slowly [J].

Drummond, DA ;

Bloom, JD ;

Adami, C ;

Wilke, CO ;

Arnold, FH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (40) :14338-14343

[8] Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor [J].

Duan, JB ;

Wainwright, MS ;

Comeron, JM ;

Saitou, N ;

Sanders, AR ;

Gelernter, J ;

Gejman, PV .

HUMAN MOLECULAR GENETICS, 2003, 12 (03) :205-216

[9] REDUCED SYNONYMOUS SUBSTITUTION RATE AT THE START OF ENTEROBACTERIAL GENES [J].

EYREWALKER, A ;

BULMER, M .

NUCLEIC ACIDS RESEARCH, 1993, 21 (19) :4599-4603

[10] Global analysis of protein expression in yeast [J].

Ghaemmaghami, S ;

Huh, W ;

Bower, K ;

Howson, RW ;

Belle, A ;

Dephoure, N ;

O'Shea, EK ;

Weissman, JS .

NATURE, 2003, 425 (6959) :737-741

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