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~22核苷酸小RNA，被认为在转录后水平上控制基因的表达。虽然miRNA介导的基因调控的重要性现在是显而易见的，因为miRNA基因在动物中扮演着不同的功能角色，但它们的作用机制仍然不清楚。我们最近发现，编码相同成熟miRNAs的miRNA基因可能具有不同的生物活性，这是由它们的同源前miRNA环决定的，揭示了在前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。在最初发现的线虫lin-4基因中，人们注意到lin-4基因的突变和缺失总是会影响包括初级 公共卫生相关性 最近的发现揭示了一个基本的遗传程序层，它由一类丰富的RNA编码基因--miRNA基因控制。在这里，我们将讨论miRNA基因的活性可能受我们发现的意想不到的调控元件控制的机制。 科学审查干事编写了以下简历部分，以总结审查委员会关于下列问题的讨论结果。 脊椎动物(简历)：可以接受 委员会预算建议： 预算是按要求建议的。 科学审查官员指出： 由于NIH主任先锋奖的申请审查方式与其他NIH拨款机制不同，因此不分配标准分数和百分位数。以上评论是面谈小组讨论的摘要。请忽略第一页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.