Beyond secondary structure: Primary-sequence determinants license Pri-miRNA hairpins for processing

Vincent C. Auyeung, Igor Ulitsky, Sean E. McGeary, David P. Bartel

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)844-858
Number of pages15
Issue number4
StatePublished - 14 Feb 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


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