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A single Hox locus in Drosophila produces functional microRNAs from opposite DNA strands
Alexander Stark1,2,6,8, Natascha Bushati3,6, Calvin H. Jan4, Pouya Kheradpour1,2, Emily Hodges5, Julius Brennecke5, David P. Bartel4, Stephen M. Cohen3,7, and Manolis Kellis1,9
1 Broad Institute of Massachussetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02141, USA; 2 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; 3 European Molecular Biology Laboratory, 69117 Heidelberg, Germany; 4 Department of Biology, Howard Hughes Medical Institute and Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology Cambridge, Massachusetts 02139, USA; 5 Watson School of Biological Sciences and Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
MicroRNAs (miRNAs) are 22-nucleotide RNAs that are processed from characteristic precursor hairpins and pair to sites in messages of protein-coding genes to direct post-transcriptional repression. Here, we report that the miRNA iab-4 locus in the Drosophila Hox cluster is transcribed convergently from both DNA strands, giving rise to two distinct functional miRNAs. Both sense and antisense miRNA products target neighboring Hox genes via highly conserved sites, leading to homeotic transformations when ectopically expressed. We also report sense/antisense miRNAs in mouse and find antisense transcripts close to many miRNAs in both flies and mammals, suggesting that additional sense/antisense pairs exist.
[Keywords: Drosophila; miR-iab-4; Hox; antisense miRNAs]]
Received September 6, 2007; revised version accepted November 2, 2007.
6 This authors contributed equally to this work.
7 Present address: Temasek Life Sciences Laboratory, The National University of Singapore, Singapore 117604.
8 Corresponding authors.