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5′UTR G-quadruplex structure enhances translation in size dependent manner

Author

Listed:
  • Chun-Ying Lee

    (Johns Hopkins University)

  • Meera Joshi

    (Johns Hopkins University)

  • Ashley Wang

    (Johns Hopkins University)

  • Sua Myong

    (Johns Hopkins University
    University of Illinois)

Abstract

Translation initiation in bacteria is frequently regulated by various structures in the 5′ untranslated region (5′UTR). Previously, we demonstrated that G-quadruplex (G4) formation in non-template DNA enhances transcription. In this study, we aim to explore how G4 formation in mRNA (RG4) at 5′UTR impacts translation using a T7-based in vitro translation system and in E. coli. We show that RG4 strongly promotes translation efficiency in a size-dependent manner. Additionally, inserting a hairpin upstream of the RG4 further enhances translation efficiency, reaching up to a 12-fold increase. We find that the RG4-dependent effect is not due to increased ribosome affinity, ribosome binding site accessibility, or mRNA stability. We propose a physical barrier model in which bulky structures in 5′UTR biases ribosome movement toward the downstream start codon, thereby increasing the translation output. This study provides biophysical insights into the regulatory role of 5′UTR structures in in vitro and bacterial translation, highlighting their potential applications in tuning gene expression.

Suggested Citation

  • Chun-Ying Lee & Meera Joshi & Ashley Wang & Sua Myong, 2024. "5′UTR G-quadruplex structure enhances translation in size dependent manner," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48247-8
    DOI: 10.1038/s41467-024-48247-8
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    References listed on IDEAS

    as
    1. Ramreddy Tippana & Michael C. Chen & Natalia A. Demeshkina & Adrian R. Ferré-D’Amaré & Sua Myong, 2019. "RNA G-quadruplex is resolved by repetitive and ATP-dependent mechanism of DHX36," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    2. Chun-Ying Lee & Christina McNerney & Kevin Ma & Walter Zhao & Ashley Wang & Sua Myong, 2020. "R-loop induced G-quadruplex in non-template promotes transcription by successive R-loop formation," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    3. Markus Sauer & Stefan A. Juranek & James Marks & Alessio Magis & Hinke G. Kazemier & Daniel Hilbig & Daniel Benhalevy & Xiantao Wang & Markus Hafner & Katrin Paeschke, 2019. "DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
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