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Article
Subject Categories: RNA
The EMBO Journal (2007) 26, 775–783, doi:10.1038/sj.emboj.7601512
Published online 25 January 2007
Processing of intronic microRNAs
Young-Kook Kim and V Narry Kim
Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea

To whom correspondence should be addressed
V Narry Kim, Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul 151-742, Korea. Tel.: +82 2 880 9120; Fax: +82 2 887 0244; E-mail: narrykim@snu.ac.kr

Received 30 May 2006; Accepted 29 November 2006; Published online 25 January 2007.
Abstract
The majority of human microRNA (miRNA) loci are located within intronic regions and are transcribed by RNA polymerase II as part of their hosting transcription units. The primary transcripts are cleaved by Drosha to release approx70 nt pre-miRNAs that are subsequently processed by Dicer to generate mature approx22 nt miRNAs. It is generally believed that intronic miRNAs are released by Drosha from excised introns after the splicing reaction has occurred. However, our database searches and experiments indicate that intronic miRNAs can be processed from unspliced intronic regions before splicing catalysis. Intriguingly, cleavage of an intron by Drosha does not significantly affect the production of mature mRNA, suggesting that a continuous intron may not be required for splicing and that the exons may be tethered to each other. Hence, Drosha may cleave intronic miRNAs between the splicing commitment step and the excision step, thereby ensuring both miRNA biogenesis and protein synthesis from a single primary transcript. Our study provides a novel example of eukaryotic gene organization and RNA-processing control.
Keywords: Drosha, intron, MicroRNA, processing, splicing
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