Nonoptimal Codon Usage Influences Protein Structure in Intrinsically Disordered Regions

Overview

Journal Mol Microbiol

Specialties Microbiology
Molecular Biology

Date 2015 Jun 3

PMID 26032251

Citations 61

Authors

Mian Zhou

Tao Wang

Jingjing Fu

Guanghua Xiao

Yi Liu

Affiliations

Soon will be listed here.

Abstract

Synonymous codons are not used with equal frequencies in most genomes. Codon usage has been proposed to play a role in regulating translation kinetics and co-translational protein folding. The relationship between codon usage and protein structures and the in vivo role of codon usage in eukaryotic protein folding is not clear. Here, we show that there is a strong codon usage bias in the filamentous fungus Neurospora. Importantly, we found genome-wide correlations between codon choices and predicted protein secondary structures: Nonoptimal codons are preferentially used in intrinsically disordered regions, and more optimal codons are used in structured domains. The functional importance of such correlations in vivo was confirmed by structure-based codon manipulation of codons in the Neurospora circadian clock gene frequency (frq). The codon optimization of the predicted disordered, but not well-structured regions of FRQ impairs clock function and altered FRQ structures. Furthermore, the correlations between codon usage and protein disorder tendency are conserved in other eukaryotes. Together, these results suggest that codon choices and protein structures co-evolve to ensure proper protein folding in eukaryotic organisms.

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References

Yang Y, He Q, Cheng P, Wrage P, Yarden O, Liu Y . Distinct roles for PP1 and PP2A in the Neurospora circadian clock. Genes Dev. 2004; 18(3):255-60. PMC: 338279. DOI: 10.1101/gad.1152604. View

Ward J, Sodhi J, McGuffin L, Buxton B, Jones D . Prediction and functional analysis of native disorder in proteins from the three kingdoms of life. J Mol Biol. 2004; 337(3):635-45. DOI: 10.1016/j.jmb.2004.02.002. View

Guo J, Cheng P, Liu Y . Functional significance of FRH in regulating the phosphorylation and stability of Neurospora circadian clock protein FRQ. J Biol Chem. 2010; 285(15):11508-15. PMC: 2857029. DOI: 10.1074/jbc.M109.071688. View

Zhou T, Weems M, Wilke C . Translationally optimal codons associate with structurally sensitive sites in proteins. Mol Biol Evol. 2009; 26(7):1571-80. PMC: 2734146. DOI: 10.1093/molbev/msp070. View

Siller E, DeZwaan D, Anderson J, Freeman B, Barral J . Slowing bacterial translation speed enhances eukaryotic protein folding efficiency. J Mol Biol. 2010; 396(5):1310-8. DOI: 10.1016/j.jmb.2009.12.042. View

Xu Y, Ma P, Shah P, Rokas A, Liu Y, Johnson C . Non-optimal codon usage is a mechanism to achieve circadian clock conditionality. Nature. 2013; 495(7439):116-20. PMC: 3593822. DOI: 10.1038/nature11942. View

Zhou M, Guo J, Cha J, Chae M, Chen S, Barral J . Non-optimal codon usage affects expression, structure and function of clock protein FRQ. Nature. 2013; 495(7439):111-5. PMC: 3629845. DOI: 10.1038/nature11833. View

Hurley J, Larrondo L, Loros J, Dunlap J . Conserved RNA helicase FRH acts nonenzymatically to support the intrinsically disordered neurospora clock protein FRQ. Mol Cell. 2013; 52(6):832-43. PMC: 3900029. DOI: 10.1016/j.molcel.2013.11.005. View

Yu C, Dang Y, Zhou Z, Wu C, Zhao F, Sachs M . Codon Usage Influences the Local Rate of Translation Elongation to Regulate Co-translational Protein Folding. Mol Cell. 2015; 59(5):744-54. PMC: 4561030. DOI: 10.1016/j.molcel.2015.07.018. View

10.

Komar A, Lesnik T, Reiss C . Synonymous codon substitutions affect ribosome traffic and protein folding during in vitro translation. FEBS Lett. 2000; 462(3):387-91. DOI: 10.1016/s0014-5793(99)01566-5. View

11.

McGuffin L, Bryson K, Jones D . The PSIPRED protein structure prediction server. Bioinformatics. 2000; 16(4):404-5. DOI: 10.1093/bioinformatics/16.4.404. View

12.

Cheng P, Yang Y, Heintzen C, Liu Y . Coiled-coil domain-mediated FRQ-FRQ interaction is essential for its circadian clock function in Neurospora. EMBO J. 2001; 20(1-2):101-8. PMC: 140186. DOI: 10.1093/emboj/20.1.101. View

13.

YOUNG M, Kay S . Time zones: a comparative genetics of circadian clocks. Nat Rev Genet. 2001; 2(9):702-15. DOI: 10.1038/35088576. View

14.

Dunker A, Obradovic Z, Romero P, Garner E, Brown C . Intrinsic protein disorder in complete genomes. Genome Inform Ser Workshop Genome Inform. 2001; 11:161-71. View

15.

Tuller T, Carmi A, Vestsigian K, Navon S, Dorfan Y, Zaborske J . An evolutionarily conserved mechanism for controlling the efficiency of protein translation. Cell. 2010; 141(2):344-54. DOI: 10.1016/j.cell.2010.03.031. View

16.

Cannarozzi G, Cannarrozzi G, Schraudolph N, Faty M, von Rohr P, Friberg M . A role for codon order in translation dynamics. Cell. 2010; 141(2):355-67. DOI: 10.1016/j.cell.2010.02.036. View

17.

Saunders R, Deane C . Synonymous codon usage influences the local protein structure observed. Nucleic Acids Res. 2010; 38(19):6719-28. PMC: 2965230. DOI: 10.1093/nar/gkq495. View

18.

Lee Y, Zhou T, Tartaglia G, Vendruscolo M, Wilke C . Translationally optimal codons associate with aggregation-prone sites in proteins. Proteomics. 2010; 10(23):4163-71. PMC: 3037288. DOI: 10.1002/pmic.201000229. View

19.

Plotkin J, Kudla G . Synonymous but not the same: the causes and consequences of codon bias. Nat Rev Genet. 2010; 12(1):32-42. PMC: 3074964. DOI: 10.1038/nrg2899. View

20.

Cha J, Yuan H, Liu Y . Regulation of the activity and cellular localization of the circadian clock protein FRQ. J Biol Chem. 2011; 286(13):11469-78. PMC: 3064202. DOI: 10.1074/jbc.M111.219782. View