The Menu of Features that Define Primary MicroRNAs and Enable De Novo Design of MicroRNA Genes
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nihms718904.pdf
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Author(s)
Fang, Wenwen
Bartel, David
Date Issued
September 2015
Journal
Molecular Cell
Publisher
Elsevier BV
Citation
Fang, Wenwen and David P. Bartel. “The Menu of Features That Define Primary MicroRNAs and Enable De Novo Design of MicroRNA Genes.” Molecular Cell 60, 1 (October 2015): 131–145 © 2015 Elsevier Inc
Version
Author's final manuscript
Abstract
MicroRNAs (miRNAs) are small regulatory RNAs processed from stem-loop regions of primary transcripts (pri-miRNAs), with the choice of stem loops for initial processing largely determining what becomes a miRNA. To identify sequence and structural features influencing this choice, we determined cleavage efficiencies of > 50,000 variants of three human pri-miRNAs, focusing on the regions intractable to previous high-throughput analyses. Our analyses revealed a mismatched motif in the basal stem region, a preference for maintaining or improving base pairing throughout the remainder of the stem, and a narrow stem-length preference of 35 ± 1 base pairs. Incorporating these features with previously identified features, including three primary-sequence motifs, yielded a unifying model defining mammalian pri-miRNAs in which motifs help orient processing and increase efficiency, with the presence of more motifs compensating for structural defects. This model enables generation of artificial pri-miRNAs, designed de novo, without reference to any natural sequence yet processed more efficiently than natural pri-miRNAs.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.MOLCEL.2015.08.015
