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A short translational ramp determines the efficiency of protein synthesis

Author

Listed:
  • Manasvi Verma

    (Washington University School of Medicine)

  • Junhong Choi

    (Stanford University School of Medicine
    Stanford University
    University of Washington)

  • Kyle A. Cottrell

    (Washington University School of Medicine)

  • Zeno Lavagnino

    (Washington University School of Medicine
    IRCCS Ospedale San Raffaele)

  • Erica N. Thomas

    (Washington University)

  • Slavica Pavlovic-Djuranovic

    (Washington University School of Medicine)

  • Pawel Szczesny

    (Institute of Biochemistry and Biophysics Polish Academy of Sciences)

  • David W. Piston

    (Washington University School of Medicine)

  • Hani S. Zaher

    (Washington University)

  • Joseph D. Puglisi

    (Stanford University School of Medicine)

  • Sergej Djuranovic

    (Washington University School of Medicine)

Abstract

Translation initiation is a major rate-limiting step for protein synthesis. However, recent studies strongly suggest that the efficiency of protein synthesis is additionally regulated by multiple factors that impact the elongation phase. To assess the influence of early elongation on protein synthesis, we employed a library of more than 250,000 reporters combined with in vitro and in vivo protein expression assays. Here we report that the identity of the amino acids encoded by codons 3 to 5 impact protein yield. This effect is independent of tRNA abundance, translation initiation efficiency, or overall mRNA structure. Single-molecule measurements of translation kinetics revealed pausing of the ribosome and aborted protein synthesis on codons 4 and 5 of distinct amino acid and nucleotide compositions. Finally, introduction of preferred sequence motifs only at specific codon positions improves protein synthesis efficiency for recombinant proteins. Collectively, our data underscore the critical role of early elongation events in translational control of gene expression.

Suggested Citation

  • Manasvi Verma & Junhong Choi & Kyle A. Cottrell & Zeno Lavagnino & Erica N. Thomas & Slavica Pavlovic-Djuranovic & Pawel Szczesny & David W. Piston & Hani S. Zaher & Joseph D. Puglisi & Sergej Djurano, 2019. "A short translational ramp determines the efficiency of protein synthesis," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13810-1
    DOI: 10.1038/s41467-019-13810-1
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    Cited by:

    1. Poonam Roshan & Sahiti Kuppa & Jenna R. Mattice & Vikas Kaushik & Rahul Chadda & Nilisha Pokhrel & Brunda R. Tumala & Aparna Biswas & Brian Bothner & Edwin Antony & Sofia Origanti, 2023. "An Aurora B-RPA signaling axis secures chromosome segregation fidelity," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Asuteka Nagao & Yui Nakanishi & Yutaro Yamaguchi & Yoshifumi Mishina & Minami Karoji & Takafumi Toya & Tomoya Fujita & Shintaro Iwasaki & Kenjyo Miyauchi & Yuriko Sakaguchi & Tsutomu Suzuki, 2023. "Quality control of protein synthesis in the early elongation stage," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Fajin Li & Jianhuo Fang & Yifan Yu & Sijia Hao & Qin Zou & Qinglin Zeng & Xuerui Yang, 2023. "Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Owain J. Bryant & Filip Lastovka & Jessica Powell & Betty Y. -W. Chung, 2023. "The distinct translational landscapes of gram-negative Salmonella and gram-positive Listeria," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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