RNA processing and gene regulation

遗传信息从DNA到RNA再到蛋白质的流动涉及复杂的调节机制，其中大部分作用于转录过程的下游，转录过程从DNA模板产生RNA分子。RNA剪接是从前体RNA中消除非编码间插序列并将编码序列连接在一起以形成成熟mRNA的过程，所述成熟mRNA从细胞核输出用于翻译以在细胞中产生蛋白质。有时，一系列不同的mRNA分子可以从相同的前体RNA产生，这一过程称为选择性剪接。这允许单个基因增加其编码能力，导致结构和功能不同形式的蛋白质的合成，影响不同的细胞过程。我们研究可变剪接的调节以及它的失调如何导致人类疾病。我们还专注于一种被称为无义介导的衰变或NMD的监视机制，该机制消除了具有提前终止密码子的mRNA，否则这些密码子会产生对细胞潜在有害的截短蛋白质。这一点很重要，因为国家导弹防御系统的反应影响到多达三分之一的人类遗传疾病的严重程度。我们希望能够更好地理解细胞RNA的产生是如何控制的，以及它的失调如何导致人类疾病。

The flow of genetic information from DNA to RNA to protein involves complex mechanisms of regulation, most of which act downstream of the process of transcription, which produces RNA molecules from a DNA template. RNA splicing is a process that eliminates non-coding intervening sequences from precursor RNAs and that joins together coding sequences to form the mature mRNA that is exported from the nucleus for translation to produce proteins in the cell. Sometimes, a series of different mRNA molecules can be produced from the same precursor RNA, in a process termed alternative splicing. This allows a single gene to increase its coding capacity, leading to the synthesis of structurally and functionally distinct forms of a protein that influence different cellular processes. We study the regulation of alternative splicing and how its misregulation can lead to human disease. We are also focusing on a surveillance mechanism, termed Nonsense-mediated decay or NMD, that eliminates mRNAs with premature termination codons that would otherwise give rise to truncated proteins that are potentially harmful for the cell. This is important since the NMD response affects the severity of up to one third of all human genetic diseases. We expect to facilitate a greater understanding of how the production of cellular RNAs is controlled, and how its dysregulation contributes to human disease.