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Human Molecular Genetics Advance Access published online on February 9, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi084
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© The Author 2005. Published by Oxford University Press. All rights reserved

Article

Natural antisense transcripts (NATs) associated with genes involved in eye development

Giovanna Alfano 1, Carmen Vitiello 1, Cristina Caccioppoli 1, Tiziana Caramico 1, Antonietta Carola 1, Michael J. Szego 2, Roderick R. McInnes 3, Alberto Auricchio 1, and Sandro Banfi 1*

1 Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80131 Naples, Italy
2 Program in Genetics and Developmental Biology, Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto
3 Program in Genetics and Developmental Biology, Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto; Departments of Pediatrics, University of Toronto, Toronto, Canada

* To whom correspondence should be addressed.
Sandro Banfi, E-mail: mailto:banfi{at}tigem.it


  Abstract

Natural antisense transcripts (NATs) are a class of genes whose role in controlling gene expression is becoming more and more relevant. We describe the identification of eight novel mouse NATs associated with transcription factors (Pax6, Pax2, Six3, Six6, Otx2, Crx, Rax and Vax2) that play an important role in eye development and function. These newly-identified NATs overlap with the mature processed mRNAs or with the primary unprocessed transcript of their corresponding sense genes, are predicted to represent either protein coding or noncoding RNAs and undergo extensive alternative splicing. Expression studies, by both RT-PCR and RNA in situ hybridization, demonstrate that most of these NATs, similarly to their sense counterparts, display a specific or predominant expression in the retina, particularly at postnatal stages. We found a significant reduction of the expression levels of one of these NATs, Vax2OS (Vax2 opposite strand) in a mouse mutant carrying the inactivation of Vax2, the corresponding sense gene. In addition, we overexpressed another NAT, CrxOS, in mouse adult retina using adeno-associated viral vectors and we observed a significant decrease in the expression levels of the corresponding sense gene, Crx. These results suggest that these transcripts are functionally related to their sense counterparts and may play an important role in regulating the molecular mechanisms that underlie eye development and function in both physiological and pathological conditions.


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