Biological functions and post-transcriptional regulation of microRNAs

MiRNAs是一种小的非编码RNA，它被装载到ArgAerte蛋白中，形成miRNA诱导的沉默复合体(MiRISC)的核心。MiRNAs引导miRISC与互补的靶mRNAs结合，使其表达沉默。MiRNA基因座的突变扰乱了基因表达程序，从而可能导致包括癌症在内的各种疾病的发展。因此，了解miRNAs在正常发育中的功能和调节miRNAs的分子机制都是至关重要的生物学问题。 了解miRNAs在胚胎发育过程中的生物学功能 虽然在线虫和其他生物中对miRNAs在分化组织中的功能进行了很好的研究，但只有少数动物的miRNAs的胚胎功能被了解。此外，在母体到受精卵的转变(MZT)之前，miRNAs如何在很大程度上对基因表达进行转录后控制是完全未知的。线虫是研究胚胎发育的良好模式生物，因为它有明确的定型细胞谱系和强大的遗传工具。我们的团队正在使用线虫来阐明miRNAs在胚胎发生中的功能，首先专注于胚胎发生所需的miRNA家族。 为了剖析由这些miRNAs控制的生物通路，我们小组正在对microRNA家族突变表型的抑制子进行正向(突变)和反向(RNAi)筛选。了解受胚胎表达的microRNA家族影响的生物网络将为如何控制基因表达以协调胚胎发生提供重要的见解。 确定miRNA和ArgAerte周转的分子机制 MiRNA生物发生和衰退速率的平衡控制miRNA的丰度，从而控制基因表达程序。以前的研究已经仔细地阐明了miRNA生物发生的机制。然而，我们对miRNAs和miRISC是如何被结构性地或以受监管的方式移交的知之甚少。这是我们对miRNA调控，从而对基因表达调控的理解的一个主要差距。在本财年，我们专注于使用深度测序来阐明非模板3添加在全球microRNA营业额中的作用。

MiRNAs are small noncoding RNAs that are loaded into Argonaute proteins to form the core of the miRNA-Induced Silencing Complex (miRISC). MiRNAs guide miRISC to complementary target mRNAs to silence their expression. Mutations in miRNA loci disrupt gene expression programs, and thus can contribute to the development of various diseases, including cancer. Consequently, understanding both the functions of miRNAs in normal development and the molecular mechanisms that regulate miRNAs are biological questions of critical importance. Understanding the biological functions of miRNAs during embryogenesis While the functions of miRNAs in differentiated tissues are well-studied in C. elegans and other organisms, the embryonic functions of only a few animal miRNAs are understood. Moreover, how miRNAs contribute to the largely post-transcriptional control of gene expression prior to the maternal-to-zygotic transition (MZT) is completely unknown. C. elegans is an excellent model organism in which to study embryonic development due to its well-defined stereotypic cell lineage and powerful genetic tools. Our group is using use C. elegans to elucidate the functions of miRNAs in embryogenesis, first focusing on the miRNA families that are required for embryogenesis. To dissect the biological pathways controlled by these miRNAs, our group is conducting forward (mutagenesis) and reverse (RNAi) screens for suppressors of microRNA family mutant phenotypes. Understanding the biological networks impacted by the embryonically-expressed microRNA families will yield important insights into how gene expression is controlled to coordinate embryogenesis. Defining the molecular mechanisms of miRNA and Argonaute turnover The balance of the rates of miRNA biogenesis and decay control miRNA abundance, and thus gene expression programs. Previous research has carefully elucidated mechanisms of miRNA biogenesis. However, we know very little about how miRNAs and miRISC are turned over either constitutively or in a regulated manner. This is a major gap in our understanding of miRNA regulation, and thus the regulation of gene expression. During this fiscal period, we have focused on using deep sequencing to elucidate the role of untemplated 3 additions in global microRNA turnover.