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RNA regulons in Hox 5′ UTRs confer ribosome specificity to gene regulation

Author

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  • Shifeng Xue

    (Stanford University
    Stanford University
    Tetrad Graduate Program, University of California, San Francisco, San Francisco, California 94158, USA)

  • Siqi Tian

    (Stanford University)

  • Kotaro Fujii

    (Stanford University
    Stanford University)

  • Wipapat Kladwang

    (Stanford University)

  • Rhiju Das

    (Stanford University
    Stanford University)

  • Maria Barna

    (Stanford University
    Stanford University)

Abstract

Emerging evidence suggests that the ribosome has a regulatory function in directing how the genome is translated in time and space. However, how this regulation is encoded in the messenger RNA sequence remains largely unknown. Here we uncover unique RNA regulons embedded in homeobox (Hox) 5′ untranslated regions (UTRs) that confer ribosome-mediated control of gene expression. These structured RNA elements, resembling viral internal ribosome entry sites (IRESs), are found in subsets of Hox mRNAs. They facilitate ribosome recruitment and require the ribosomal protein RPL38 for their activity. Despite numerous layers of Hox gene regulation, these IRES elements are essential for converting Hox transcripts into proteins to pattern the mammalian body plan. This specialized mode of IRES-dependent translation is enabled by an additional regulatory element that we term the translation inhibitory element (TIE), which blocks cap-dependent translation of transcripts. Together, these data uncover a new paradigm for ribosome-mediated control of gene expression and organismal development.

Suggested Citation

  • Shifeng Xue & Siqi Tian & Kotaro Fujii & Wipapat Kladwang & Rhiju Das & Maria Barna, 2015. "RNA regulons in Hox 5′ UTRs confer ribosome specificity to gene regulation," Nature, Nature, vol. 517(7532), pages 33-38, January.
    • Handle: RePEc:nat:nature:v:517:y:2015:i:7532:d:10.1038_nature14010
    DOI: 10.1038/nature14010
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    Cited by:

    1. Claudia M. Fusco & Kristina Desch & Aline R. Dörrbaum & Mantian Wang & Anja Staab & Ivy C. W. Chan & Eleanor Vail & Veronica Villeri & Julian D. Langer & Erin M. Schuman, 2021. "Neuronal ribosomes exhibit dynamic and context-dependent exchange of ribosomal proteins," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

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