Natural antisense transcripts associated with genes involved in eye development
Natural antisense transcripts associated with genes involved in eye development
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DOI：
10.1093/hmg/ddi084
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发表时间：
2005-04-01
影响因子：
3.5
通讯作者：
Banfi, S
中科院分区：
文献类型：
--
作者：
Alfano, G;Vitiello, C;Banfi, S
天然反义转录本(NAT)是一类基因，其在基因表达调控中的作用越来越重要。我们描述了8个与转录因子(Pax6、Pax2、Six3、Six6、OTX2、CRX、Rax和Vax2)相关的新的小鼠NAT的鉴定，它们在眼睛的发育和功能中发挥着重要作用。这些新发现的NAT与成熟的已处理mRNAs或其相应正义基因的初级未处理转录本重叠，被预测为代表蛋白质编码或非编码RNA，并经历广泛的选择性剪接。通过RT-PCR和RNA原位杂交的表达研究表明，这些NAT中的大多数类似于它们的正义对应物，在视网膜中显示特定或优势表达，特别是在出生后阶段。我们发现，在携带相应正义基因Vax2失活的小鼠突变体中，其中一种NAT Vax2OS(Vax2相反链)的表达水平显著降低。此外，我们使用腺相关病毒载体在小鼠成年视网膜中过表达了另一种NAT，CrxOS，我们观察到相应正义基因CRx的表达水平显著降低。这些结果表明，这些转录本在功能上与它们的正义转录本相关，并可能在调节生理和病理条件下眼睛发育和功能的分子机制中发挥重要作用。
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.