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Nucleic acids research v.45 no.2, 2017년, pp.1015 - 1025   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Minimum-noise production of translation factor eIF4G maps to a mechanistically determined optimal rate control window for protein synthesis

Meng, Xiang (Warwick Integrative Synthetic Biology Centre (WISB) and School of Life Sciences, University of Warwick, Gibbet Hill, Coventry CV4 7AL, UK ); Firczuk, Helena (Warwick Integrative Synthetic Biology Centre (WISB) and School of Life Sciences, University of Warwick, Gibbet Hill, Coventry CV4 7AL, UK ); Pietroni, Paola (Warwick Integrative Synthetic Biology Centre (WISB) and School of Life Sciences, University of Warwick, Gibbet Hill, Coventry CV4 7AL, UK ); Westbrook, Richard (Warwick Integrative Synthetic Biology Centre (WISB) and School of Life Sciences, University of Warwick, Gibbet Hill, Coventry CV4 7AL, UK ); Dacheux, Estelle (Warwick Integrative Synthetic Biology Centre (WISB) and School of Life Sciences, University of Warwick, Gibbet Hill, Coventry CV4 7AL, UK ); Mendes, Pedro (Center for Quantitative Medicine, UConn Health, 263 Farmington Avenue, CT 06030-6033, USA ); McCarthy, John E.G. (Warwick Integrative Synthetic Biology Centre (WISB) and School of Life Sciences, University of Warwick, Gibbet Hill, Coventry CV4 7AL, UK );
  • 초록  

    Gene expression noise influences organism evolution and fitness. The mechanisms determining the relationship between stochasticity and the functional role of translation machinery components are critical to viability. eIF4G is an essential translation factor that exerts strong control over protein synthesis. We observe an asymmetric, approximately bell-shaped, relationship between the average intracellular abundance of eIF4G and rates of cell population growth and global mRNA translation, with peak rates occurring at normal physiological abundance. This relationship fits a computational model in which eIF4G is at the core of a multi-component–complex assembly pathway. This model also correctly predicts a plateau-like response of translation to super-physiological increases in abundance of the other cap-complex factors, eIF4E and eIF4A. Engineered changes in eIF4G abundance amplify noise, demonstrating that minimum stochasticity coincides with physiological abundance of this factor. Noise is not increased when eIF4E is overproduced. Plasmid-mediated synthesis of eIF4G imposes increased global gene expression stochasticity and reduced viability because the intrinsic noise for this factor influences total cellular gene noise. The naturally evolved eIF4G gene expression noise minimum maps within the optimal activity zone dictated by eIF4G's mechanistic role. Rate control and noise are therefore interdependent and have co-evolved to share an optimal physiological abundance point.


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