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The formation of intramolecular secondary structure brings mRNA ends in close proximity

Wan-Jung C. Lai, Mohammad Kayedkhordeh, Erica V. Cornell, Elie Farah, Stanislav Bellaousov, Robert Rietmeijer, David H. Mathews, Dmitri N. Ermolenko
doi: https://doi.org/10.1101/289496
Wan-Jung C. Lai
Department of Biochemistry & Biophysics and Center for RNA Biology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642
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Mohammad Kayedkhordeh
Department of Biochemistry & Biophysics and Center for RNA Biology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642
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Erica V. Cornell
Department of Biochemistry & Biophysics and Center for RNA Biology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642
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Elie Farah
Department of Biochemistry & Biophysics and Center for RNA Biology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642
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Stanislav Bellaousov
Department of Biochemistry & Biophysics and Center for RNA Biology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642
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Robert Rietmeijer
Department of Biochemistry & Biophysics and Center for RNA Biology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642
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David H. Mathews
Department of Biochemistry & Biophysics and Center for RNA Biology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642
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  • For correspondence: David_Mathews@URMC.Rochester.edu Dmitri_Ermolenko@URMC.Rochester.edu
Dmitri N. Ermolenko
Department of Biochemistry & Biophysics and Center for RNA Biology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642
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  • For correspondence: David_Mathews@URMC.Rochester.edu Dmitri_Ermolenko@URMC.Rochester.edu
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ABSTRACT

A number of protein factors regulate protein synthesis by bridging mRNA ends or untranslated regions (UTRs). Using experimental and computational approaches, we show that mRNAs from various organisms, including humans, have an intrinsic propensity to fold into structures in which the 5’ end and 3’ end are ≤ 7 nm apart irrespective of mRNA length. Computational estimates performed for ∼22,000 human transcripts indicate that the inherent proximity of the ends is a universal property of most, if not all, mRNA sequences. Only specific RNA sequences, which have low sequence complexity and are devoid of guanosines, are unstructured and exhibit end-to-end distances expected for the random coil conformation of RNA. Our results suggest that the intrinsic proximity of mRNA ends may facilitate binding of translation factors that bridge mRNA 5’ and 3’ UTRs. Furthermore, our studies provide the basis for measuring, computing and manipulating end-to-end distances and secondary structure in mRNAs in research and biotechnology.

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Posted March 27, 2018.
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The formation of intramolecular secondary structure brings mRNA ends in close proximity
Wan-Jung C. Lai, Mohammad Kayedkhordeh, Erica V. Cornell, Elie Farah, Stanislav Bellaousov, Robert Rietmeijer, David H. Mathews, Dmitri N. Ermolenko
bioRxiv 289496; doi: https://doi.org/10.1101/289496
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The formation of intramolecular secondary structure brings mRNA ends in close proximity
Wan-Jung C. Lai, Mohammad Kayedkhordeh, Erica V. Cornell, Elie Farah, Stanislav Bellaousov, Robert Rietmeijer, David H. Mathews, Dmitri N. Ermolenko
bioRxiv 289496; doi: https://doi.org/10.1101/289496

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