Article
- The EMBO Journal (2005) 24, 138 - 148
- doi:10.1038/sj.emboj.7600491
Published online: 25 November 2004
Subject Category:
Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha
Yan Zeng1, Rui Yi2,a and Bryan R Cullen1,2
- Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC, USA
- Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA
Correspondence to:
Bryan R Cullen, Duke University Medical Center, Box 3025, Durham, NC 27710, USA. Tel.: +1 919 684 3369; Fax: +1 919 681 8979; E-mail: culle002@mc.duke.edu
aPresent address: Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY, USA
Received 4 October 2004; Accepted 3 November 2004
Abstract
A critical step during human microRNA maturation is the processing of the primary microRNA transcript by the nuclear RNaseIII enzyme Drosha to generate the 
60-nucleotide precursor microRNA hairpin. How Drosha recognizes primary RNA substrates and selects its cleavage sites has remained a mystery, especially given that the known targets for Drosha processing show no discernable sequence homology. Here, we show that human Drosha selectively cleaves RNA hairpins bearing a large (
10 nucleotides) terminal loop. From the junction of the loop and the adjacent stem, Drosha then cleaves approximately two helical RNA turns into the stem to produce the precursor microRNA. Beyond the precursor microRNA cleavage sites, approximately one helix turn of stem extension is also essential for efficient processing. While the sites of Drosha cleavage are determined largely by the distance from the terminal loop, variations in stem structure and sequence around the cleavage site can fine-tune the actual cleavage sites chosen.
Keywords:
- Drosha,
- microRNA,
- RNA III enzymes,
- RNA interference,
- RNA processing
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