Multiple products from functional RNA gene loci

RNA最常见的作用是作为将DNA中的遗传信息解码为蛋白质的中间物，这些蛋白质在细胞中执行大多数已知的结构和功能角色。其他几种功能性RNA （fRNA）分子，如转移RNA、核糖体RNA和剪接体RNA，都是从它们自己的基因（所谓的RNA基因）中表达出来的，但长期以来被认为是不寻常的特殊情况。然而，越来越清楚的是，RNA分子具有许多以前无法想象的功能，包括调控基因表达，作为引导分子，在印迹，剂量补偿，催化和结构。特定的RNA类别也与包括癌症在内的疾病有关。许多新的RNA类别已经被发现，包括microrna（2001年），riboswitches（2002年）和piwi-associated RNA（2006年）。超过2000个功能性RNA基因现在可以在人类基因组中被识别出来，约占基因总数的10%。虽然在鉴定新rna方面取得了快速进展，但大多数新发现的功能尚不清楚。此外，计算研究和大规模转录数据预测，大多数RNA基因仍有待发现。有迹象表明，RNA基因可能和蛋白质编码基因一样多。正如后基因组科学开始理解基因组中编码的整套蛋白质结构和功能一样，RNA在调节细胞过程中的重要性也变得越来越清楚。以前的工作（包括我们自己的工作）表明，许多种类的功能性RNA分子是由基因位点表达的，这些基因位点也可以产生蛋白质或其他RNA产物。这一观察结果从根本上挑战了我们的基因概念。例如，敲除一个基因的研究人员可能会假设观察到的表型是蛋白质功能丧失的结果。然而，一个被忽视的fRNA产物，如microRNA，从同一位点表达，可能调节其他基因的表达，混淆了实验数据的解释。本研究旨在利用基因组中RNA基因位点的背景来了解它们的功能。例如，如果单个基因或转录物在相同的细胞中，在相同的条件下同时产生功能RNA和翻译蛋白，我们预测RNA和蛋白质将具有相关的功能，或参与相关的途径。一些已知的例子，如核糖体蛋白基因内含子表达的小核仁rna，表明情况就是如此，但尚未有大规模系统研究报道。这项工作将检验内含子rna是否确实是由宿主转录本加工的，还是由它们自己的启动子表达的。我们将测试共表达的RNA和蛋白产物是否在相同的途径中起作用。最后，我们将利用我们对内含子RNA特性的改进理解来预测新的功能RNA。

The most commonly understood role of RNA is as an intermediate in the decoding of genetic information in DNA into the proteins that carry out the majority of known structural and functional roles in the cell. A few other classes of functional RNA (fRNA) molecules, such as transfer RNAs, ribosomal RNAs and spliceosomal RNAs, are expressed from their own genes (so-called RNA genes), but were long assumed to be unusual specialised cases. However, it is becoming clear that RNA molecules have many previously unimagined functions, including regulation of gene expression, as guide molecules, in imprinting, dosage compensation, catalysis and structure. Particular RNA classes have also been implicated in disease, including cancer. A number of new RNA classes have been discovered, including microRNAs (in 2001), riboswitches (in 2002) and piwi-associated RNAs (in 2006). Over 2000 functional RNA genes can now be identified in the human genome, making up around 10% of the total gene count. While there has been rapid progress in identifying novel RNAs, the functions of the majority of new discoveries are unknown. In addition, computational studies and large-scale transcriptional data predict that the majority of RNA genes remain to be discovered. There are hints that there may be as many RNA genes as there are protein-coding genes. Just as post-genomic science begins to approach understanding of the complete set of protein structures and functions encoded in the genome, the importance of the roles of RNA in regulating cellular processes is becoming clear. Previous work (including our own) has shown that many classes of functional RNA molecules are expressed from gene loci that also make proteins or other RNA products. This observation fundamentally challenges our concept of the gene. For example, a researcher who knocks-out a gene will likely assume that an observed phenotype is the result of loss of protein function. However, an ignored fRNA product, such as a microRNA, expressed from the same locus may regulate the expression of other genes, confounding the interpretation of experimental data. The proposed research aims to use the context of RNA gene loci in the genome to understand their function. For example, if a single gene or transcript produces a functional RNA and a translated protein at the same time in the same cells under the same conditions, we predict that the RNA and protein will have related functions, or be involved in related pathways. A few known examples, such as small nucleolar RNAs expressed from introns of ribosomal protein genes, suggest that this is the case, but no large-scale systematic study has been reported. The work will examine whether intronic RNAs are indeed processed from the host transcript, or expressed from their own promoters. We will test whether co-expressed RNA and protein products function in the same pathways. Finally, we will use our improved understanding of intronic RNA characteristics to predict novel functional RNAs.