Beyond Secondary Structure: Primary-Sequence Determinants License Pri-miRNA Hairpins for Processing
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Bartel_Beyond secondary.pdf
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Author(s)
Auyeung, Vincent C.
Ulitsky, Igor
McGeary, Sean Edward
Bartel, David
Auyeung, Vincent C.
Date Issued
February 2013
Journal
Cell
Publisher
Elsevier
Citation
Auyeung, Vincent C., Igor Ulitsky, Sean E. McGeary, and David P. Bartel. “Beyond Secondary Structure: Primary-Sequence Determinants License Pri-miRNA Hairpins for Processing.” Cell 152, no. 4 (February 2013): 844–858.
Version
Author's final manuscript
Abstract
To use microRNAs to downregulate mRNA targets, cells must first process these ∼22 nt RNAs from primary transcripts (pri-miRNAs). These transcripts form RNA hairpins important for processing, but additional determinants must distinguish pri-miRNAs from the many other hairpin-containing transcripts expressed in each cell. Illustrating the complexity of this recognition, we show that most Caenorhabditis elegans pri-miRNAs lack determinants required for processing in human cells. To find these determinants, we generated many variants of four human pri-miRNAs, sequenced millions that retained function, and compared them with the starting variants. Our results confirmed the importance of pairing in the stem and revealed three primary-sequence determinants, including an SRp20-binding motif (CNNC) found downstream of most pri-miRNA hairpins in bilaterian animals, but not in nematodes. Adding this and other determinants to C. elegans pri-miRNAs imparted efficient processing in human cells, thereby confirming the importance of primary-sequence determinants for distinguishing pri-miRNAs from other hairpin-containing transcripts.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution-Noncommercial-NoDerivatives
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DOI of Published Version
https://doi.org/10.1016/j.cell.2013.01.031
