Natural antisense transcripts associated with genes involved in eye development.
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 non-coding 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.
Alfano
Giovanna
G
Telethon Institute of Genetics and Medicine, Via Pietro Castellino 111, 80131 Naples, Italy.
Vitiello
Carmen
C
Caccioppoli
Cristina
C
Caramico
Tiziana
T
Carola
Antonietta
A
Szego
Michael J
MJ
McInnes
Roderick R
RR
Auricchio
Alberto
A
Banfi
Sandro
S
D017398:Alternative Splicing; D000818:Animals; D019295:Computational Biology; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D005123:Eye / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D016678:Genome; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000196:embryology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism
D018076:DNA, Complementary; D018398:Homeodomain Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D015534:Trans-Activators; C120595:Vax2 protein, mouse; C109288:cone rod homeobox protein