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Structures of microRNA-precursor apical junctions and loops reveal non-canonical base pairs important for processing

Grant M. Shoffner, Zhixiang Peng, View ORCID ProfileFeng Guo
doi: https://doi.org/10.1101/2020.05.05.078014
Grant M. Shoffner
Department of Biological Chemistry, David Geffen School of Medicine, The Molecular Biology Institute, University of California, Los Angeles, CA 90095, U.S.A.
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Zhixiang Peng
Department of Biological Chemistry, David Geffen School of Medicine, The Molecular Biology Institute, University of California, Los Angeles, CA 90095, U.S.A.
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Feng Guo
Department of Biological Chemistry, David Geffen School of Medicine, The Molecular Biology Institute, University of California, Los Angeles, CA 90095, U.S.A.
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  • ORCID record for Feng Guo
  • For correspondence: fguo@mbi.ucla.edu
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Abstract

Metazoan pri-miRNAs and pre-miRNAs fold into characteristic hairpins that are recognized by the processing machinery. Essential to the recognition of these miR-precursors are their apical junctions where double-stranded stems meet single-stranded hairpin loops. Little is known about how apical junctions and loops fold in three-dimensional space. Here we developed a scaffold-directed crystallography method and determined the structures of eight human miR-precursor apical junctions and loops. Six structures contain non-canonical base pairs stacking on top of the hairpin stem. U-U pair contributes to thermodynamic stability in solution and is highly enriched at human miR-precursor apical junctions. Our systematic mutagenesis shows that U-U is among the most efficiently processed variants. The RNA-binding heme domain of pri-miRNA-processing protein DGCR8 binds longer loops more tightly and non-canonical pairs at the junction appear to modulate loop length. Our study provides structural and biochemical bases for understanding miR-precursors and molecular mechanisms of microRNA maturation.

Competing Interest Statement

F.G. and G.M.S. filed a provisional patent that includes the scaffold-directed crystallography method. All authors have no other competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 05, 2020.
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Structures of microRNA-precursor apical junctions and loops reveal non-canonical base pairs important for processing
Grant M. Shoffner, Zhixiang Peng, Feng Guo
bioRxiv 2020.05.05.078014; doi: https://doi.org/10.1101/2020.05.05.078014
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Structures of microRNA-precursor apical junctions and loops reveal non-canonical base pairs important for processing
Grant M. Shoffner, Zhixiang Peng, Feng Guo
bioRxiv 2020.05.05.078014; doi: https://doi.org/10.1101/2020.05.05.078014

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