Post-transcriptional regulation of Gene Expression

从DNA到RNA再到蛋白质的遗传信息流涉及到作用于转录过程下游的复杂调控机制，转录过程从DNA模板产生RNA分子。前-mRNA剪接是从前体RNA中切下非编码插入序列(内含子)，然后将编码序列(外显子)连接起来形成成熟的信使RNA的过程。选择性剪接增加了更高水平的复杂性，其中一系列不同的信使核糖核酸分子可以通过在前信使核糖核酸中不同剪接位点的不同使用而产生，从而使单个基因能够增加其编码能力。我们将研究选择性剪接的调控，特别是与其与转录过程耦合有关的调控。我们正在研究一种控制细胞产生的RNA质量的细胞过程，称为无义介导的衰退(NMD)，它降解为细胞编码有害蛋白质的RNA。我们将专注于一种专门的NMD机制，该机制定位于内质网(ER)，并在细胞应激中发挥作用。最后，我们将研究从较长的复杂折叠的前体产生短的非编码RNA(称为microRNAs)的机制，并调节细胞mRNAs的表达。我们的研究计划是最基本的。我们希望有助于更好地理解细胞RNA的产生是如何受到严格控制的，以及它的失调是如何导致人类疾病的。我们依赖于各种实验系统，包括培养中的哺乳动物细胞系、线虫(线虫)和小鼠模型，我们使用细胞生物学、生化和单分子方法。

The flow of genetic information from DNA to RNA to protein involves complex mechanisms of regulation acting downstream of the process of transcription, which produces RNA molecules from a DNA template. Pre-mRNA splicing is the process by which non-coding intervening sequences (introns) are excised from precursor RNAs and coding sequences (exons) are joined to form the mature messenger RNA. A further level of complexity is added by alternative splicing, where a series of different mRNA molecules can be produced by the differential use of splice sites within a pre-mRNA, enabling a single gene to increase its coding capacity. We will study the regulation of Alternative splicing, in particular related to its coupling to the process of transcription. We are investigating a cellular process that controls the quality of RNA produced by cells, termed Nonsense-mediated decay (NMD), which degrades RNAs that encode harmful proteins for the cell. We will focus on a specialised NMD machinery that is localised to the endoplasmic reticulum (ER) and has a role during cellular stress. Finally, we will study the mechanism by which short non-coding RNAs (termed microRNAs) are produced from longer intricately folded precursors and regulate the expression of cellular mRNAs. Our research programme is at the basic end of the spectrum. We expect to contribute to a greater understanding on how the production of cellular RNAs is tightly controlled and how its dysregulation can contribute to human disease. We rely on a variety of experimental systems, including mammalian cell lines in culture, nematodes (C. elegans) and mouse models and we use cell biological, biochemical and single-molecule approaches.