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Nucleic Acids Research 2005 33(3):1077-1086; doi:10.1093/nar/gki250
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Published online 18 February 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

Article

The mouse RNase 4 and RNase 5/ang 1 locus utilizes dual promoters for tissue-specific expression

Kimberly D. Dyer* and Helene F. Rosenberg

Laboratory of Allergic Diseases NIAID, NIH, Bethesda, MD 20892, USA

*To whom correspondence should be addressed at 10 Center Drive MSC 1886, Building 10 Room 11C216, Bethesda, MD 20892-1886, USA. Tel: +1 301 402 429; Fax: +1 301 402 4369; Email: kdyer{at}niaid.nih.gov

Received November 19, 2004. Revised January 25, 2005. Accepted January 25, 2005.

The ribonuclease A (RNase A) superfamily has been the subject of extensive studies in the areas of protein evolution, structure and biochemistry and are exciting molecules in that they appear to be responding to unique selection pressures, generating proteins capable of multiple and diverse activities. The RNase 4 and RNase 5/ang 1 shared locus breaks a pattern that is otherwise canonical among the members of the RNase A gene superfamily. Conserved among humans, mice and rats, the locus includes two non-coding exons followed by two distinct exons encoding RNase 4 and RNase 5/ang 1. Transcription from this locus is controlled by differential splicing and tissue-specific expression from promoters located 5' to each of the non-coding exons. Promoter 1, 5' to exon I, is universally active, while Promoter 2, 5' to exon II, is active only in hepatic cells in promoter assays in vitro. Transcription from Promoter 2 is dependent on an intact HNF-1 consensus binding site which binds the transcription factor HNF-1{alpha}. In summary, RNase 4 and RNase 5/ang 1 are unique among the RNase A ribonuclease genes in that they maintain a complex gene locus that is conserved across species with transcription initiated from tissue-specific dual promoters followed by differential exon splicing.

DDBJ/EMBL/GenBank accession no. AY762362


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