Functionally distinct regulatory RNAs generated by bidirectional transcription and processing of microRNA loci

Tyler, D. M., Okamura, K., Chung, W. J., Hagen, J. W., Berezikov, E., Hannon, G. J., Lai, E. C. (2008) Functionally distinct regulatory RNAs generated by bidirectional transcription and processing of microRNA loci. Genes and Development, 22 (1). pp. 26-36. ISSN 08909369 (ISSN)

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Abstract

Many microRNA (miRNA) loci exhibit compelling hairpin structures on both sense and antisense strands; however, the possibility that a miRNA gene might produce functional species from its antisense strand has not been examined. We report here that antisense transcription of the Hox miRNA locus mir-iab-4 generates the novel pre-miRNA hairpin mir-iab-8, which is then processed into endogenous mature miRNAs. Sense and antisense iab-4/iab-8 miRNAs are functionally distinguished by their distinct domains of expression and targeting capabilities. We find that miR-iab-8-5p, like miR-iab-4-5p, is also relevant to Hox gene regulation. Ectopic mir-iab-8 can strongly repress the Hox genes Ultrabithorax and abdominal-A via extensive arrays of conserved target sites, and can induce a dramatic homeotic transformation of halteres into wings. We generalize the antisense miRNA principle by showing that several other loci in both invertebrates and vertebrates are endogenously processed on their antisense strands into mature miRNAs with distinct seeds. These findings demonstrate that antisense transcription and processing contributes to the functional diversification of miRNA genes. © 2008 by Cold Spring Harbor Laboratory Press.

Item Type:	Paper
Uncontrolled Keywords:	Antisense BX-C Homeotic gene MicroRNA Hox protein protein mir iab 4 unclassified drug article gene control gene expression genetic transcription genetic variability in vivo study nonhuman priority journal Animals Base Sequence Body Patterning Drosophila Drosophila Proteins Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect In Situ Hybridization MicroRNAs Models, Genetic Molecular Sequence Data Nuclear Proteins Regulatory Sequences, Ribonucleic Acid RNA Processing, Post-Transcriptional Transcription Factors Invertebrata Vertebrata
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
CSHL Authors:	Hannon, Gregory J.
Communities:	CSHL labs > Hannon lab
Depositing User:	Matt Covey
Date:	2008
Date Deposited:	09 Jan 2013 16:41
Last Modified:	14 Jan 2013 22:04
PMCID:	PMC2151012
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/26445

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