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Cell. 2013 Feb 14;152(4):844-58. doi: 10.1016/j.cell.2013.01.031.

Beyond secondary structure: primary-sequence determinants license pri-miRNA hairpins for processing.

Author information

1
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

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.

PMID:
23415231
PMCID:
PMC3707628
DOI:
10.1016/j.cell.2013.01.031
[Indexed for MEDLINE]
Free PMC Article

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