The Role of Pre-miRNA Loop in Target Regulation by microRNA Genes

描述 摘要 MicroRNA（miRNA）基因编码一类丰富的约22个核苷酸的小RNA，被认为在转录后水平控制基因表达。尽管miRNA介导的基因调控的重要性现在是显而易见的，但由于miRNA基因在动物中显示出多种功能作用，其作用机制仍然难以捉摸。我们最近发现，编码相同成熟miRNA的miRNA基因可能具有不同的生物活性，这些生物活性由其同源的pre-miRNA环决定，揭示了pre-miRNA环中编码的意想不到的调控复杂性。这些发现促使我们重新审视miRNA领域的一些基本假设。在C.线虫lin-4基因lin-4基因中的突变和缺失总是影响包括主要的 公共卫生相关性 最近的发现揭示了由大量RNA编码基因--miRNA基因--控制的遗传程序的基本层。在这里，我们将解决的机制，miRNA基因的活性可能是由我们发现的意想不到的调控元件控制。 以下简历部分由科学审查干事编写，概述了审查委员会就以下问题进行讨论的结果。 脊椎动物（简历）：可接受 委员会的预算建议： 预算是按要求提出的。 科学审查官员注意到： 由于美国国立卫生研究院院长先锋奖的申请审查不同于其他美国国立卫生研究院拨款机制，标准分数和评分不分配。 以上评论是面试小组讨论的摘要。 请忽略第一页上的行政预算说明和下面关于重新提交（以前称为修订）申请的通知，因为它们不适用于先锋奖。

DESCRIPTION Abstract MicroRNA (miRNA) genes encode an abundant class of ~22-nucleotide small RNAs that are thought to control gene expression at the post-transcriptional levels. Although the importance of miRNA-mediated gene regulation is now evident, as miRNA genes were shown to play diverse functional roles in animals, their mechanisms of action remain elusive. We have recently found that miRNA genes encoding identical mature miRNAs could have distinct biological activities that are determined by their cognate pre-miRNA loops, revealing unexpected regulatory complexity encoded in the pre-miRNA loops. These findings prompted us to reexamine some of the fundamental assumptions in the miRNA field. It was noted in the original discovery of the C. elegans lin-4 gene that mutations and deletions in lin-4 genes invariably affect including the primary Public Health Relevance Recent discoveries have revealed a fundamental layer of genetic programs controlled by an abundant class of RNA coding genes -- the miRNA genes. Here we will address the mechanisms by which the activity of miRNA genes may be controlled by the unexpected regulatory elements that we have discovered. THE FOLLOWING RESUME SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE ON THE FOLLOWING ISSUES. VERTEBRATE ANIMAL (Resume): ACCEPTABLE COMMITTEE BUDGET RECOMMENDATIONS: The budget was recommended as requested. SCIENTIFIC REVIEW OFFICERS NOTES: Since the NIH Director's Pioneer Award applications are reviewed differently from other NIH grant mechanisms, criterion scores and percentiles are not assigned. The comments above represent a summary of the discussion by the interview panel. Please ignore the Administrative Budget Note on page one and the Notice below regarding resubmissions (formerly termed amended) applications as they do not apply to Pioneer Awards.