RNA interference is not involved in natural antisense mediated regulation of gene expression in mammals

Mohammad Ali Faghihi¹^,2 and Claes Wahlestedt¹

¹Department of Biochemistry, The Scripps Research Institute, 5353 Parkside Drive, Jupiter, FL 33458, USA

²Center for Genomics and Bioinformatics, Karolinska Institutet, Berzelius väg, SE-171 77 Stockholm, Sweden

author email corresponding author email

Genome Biology 2006, 7:R38doi:10.1186/gb-2006-7-5-r38


Published:	9 May 2006

Subject areas: Molecular biology, Cell biology

Abstract

Background

Antisense transcription, yielding both coding and non-coding RNA, is a widespread phenomenon in mammals. The mechanism by which natural antisense transcripts (NAT) may regulate gene expression are largely unknown. The aim of the present study was to explore the mechanism of reciprocal sense-antisense (S-AS) regulation by studying the effects of a coding and non-coding NAT on corresponding gene expression, and to investigate the possible involvement of endogenous RNA interference (RNAi) in S-AS interactions.

Results

We have examined the mechanism of S-AS RNA base pairing, using thymidylate synthase and hypoxia inducible factor-1α as primary examples of endogenous genes with coding and non-coding NAT partners, respectively. Here we provide direct evidence against S-AS RNA duplex formation in the cytoplasm of human cells and subsequent activation of RNAi.

Conclusion

Collectively, our data demonstrate that NAT regulation of gene expression occurs through a pathway independent of Dicer associated RNAi. Moreover, we introduce an experimental strategy with utility for the functional examination of other S-AS pair interactions.