Overlapping cistrons in a family of ion channel genes

 描述（由申请人提供）：我们发现编码P/Q型电压门控钙通道（VGCC）的CACNA 1A基因是双顺反子的。CACNA 1 A mRNA编码α 1 A亚基和第二种蛋白质α 1 ACT，α 1 ACT是一种转录因子，由于隐蔽的内部核糖体进入位点（IRES），其被翻译为第二个开放阅读框。在相同的细胞mRNA中同时表达两种蛋白质，其中一种是转录因子，可能是钙通道和其他细胞基因用于协调基因系综表达的有力策略。为了了解这类新的IRES和双顺反子基因，我们将：1。确定CACNA 1A IRES如何受RNA结合蛋白和miRNA的调控; 2.定义VGCC家族双顺反子基因的新特性。3.确定双顺反子基因表达的改变是否会导致VGCC疾病的复杂表型。这项研究将有助于我们了解双顺反子细胞基因的生物学，特别是在其他VGCC中，IRES调节机制和它们编码的蛋白质的性质，以及在复杂的人类遗传疾病的发病机制和治疗中的可能作用。

 DESCRIPTION (provided by applicant): We have discovered that the CACNA1A gene, which encodes the P/Q type voltage gated calcium channel (VGCC) is bicistronic. The CACNA1A mRNA encodes both the a1A subunit and a second protein, a1ACT, a transcription factor, that is translated as a second open reading frame due to a cryptic internal ribosomal entry site (IRES). Simultaneous expression of two proteins in the same cellular mRNA, one of which is a transcription factor, may be a powerful strategy used by calcium channels and other cellular genes to coordinate expression of an ensemble of genes. To understand this new class of IRES and bicistronic genes we will: 1. Determine how the CACNA1A IRES is regulated by RNA-binding proteins and miRNAs; 2. Define the novel properties of bicistronic genes of the VGCC family. 3. Determine whether altered bicistronic gene expression leads to the complex phenotypes of VGCC disorders. This study will help us to understand the biology of bicistronic cellular genes in particular among other VGCCs, the nature of the IRES regulatory mechanisms and proteins they encode, and the possible role in the pathogenesis and treatment of complex human genetic disease.