Post-transcriptional control of gene expression

描述（由申请人提供）：我们要求部分支持FASEB会议“基因表达的转录后调控：mRNA衰变的机制”，会议将于2004年6月26日至7月1日在亚利桑那州图森举行。mRNA的周转是基因表达的关键调控因子，但通常不被认识，因为mRNA的稳定性决定了其最终的稳态水平。此外，程序性不稳定性是抑制基因表达的重要机制。此外，越来越多的人认识到，大多数生物体采用mRNA质量监测手段，以确保只有“合适”的转录本离开细胞核并被翻译。靶向mRNA的转换是这一过程的组成部分。最后，新发现的反义调控手段，包括RNA干扰，依赖于选择性mRNA转换来实现其生物学后果。由于这些原因，mRNA的转换引起了生命科学各个领域的高度关注。本次FASEB会议的独特之处在于专注于mRNA的衰变，从而在不同的生物学环境中探索细胞和分子水平上支持这一普遍过程的机制。这次会议特别值得注意的是，它吸引了研究原核和真核生物的研究人员，并将重点放在rna与衰变装置相互作用的机制和调节衰变的因素上。会议的前三分之一将探讨我们对mRNA衰变酶最初如何与其靶标相互作用的理解的最新进展。这种相互作用主要发生在rna的末端，通常涉及高度保守的蛋白质或蛋白质复合物，但有许多令人惊讶的曲折。我们预计，对这些相互作用的非常需要的结构性调查将取得成果，并在拟议的会议上首次提出。会议的第二部分将集中讨论新生mrna、降解机制、核出口、质量控制和翻译之间的复杂相互作用。了解这些过程及其相互作用对生长、发育和疾病的调节具有无数的意义。会议的最后部分将集中于RNA干扰的机制（与现象学相反）和应用全局方法来理解mRNA衰变及其对整个细胞的影响。会议将对这一激动人心的领域的最新进展提供一个极好的概述，并将推动其下一阶段的发展。

DESCRIPTION (provided by applicant): We are requesting partial support for a FASEB Conference on "post-transcriptional regulation of gene expression: mechanisms of mRNA decay" to be held in Tucson AZ on June 26-July 1, 2004. Turnover of mRNA is a key, but frequently unrecognized, regulator of gene expression as the stability of an mRNA dictates its ultimate steady-state level. Moreover, programmed instability is an important mechanism of repressing gene expression. In addition, it is increasingly recognized that most organisms employ means of surveillance of mRNA quality to ensure that only "fit" transcripts exit the nucleus and are translated. Targeted mRNA turnover is integral to this process. Finally, newly discovered means of antisense regulation, including RNA interference, rely on selective mRNA turnover for their biological consequences. For these reasons, mRNA turnover is attracting heightened interest from all areas of the life sciences. The proposed FASEB conference is unique in concentrating on mRNA decay, thereby exploring in diverse biological settings the mechanisms, both at the cellular and molecular levels, that underpin this universal process. The proposed meeting is particularly noteworthy in attracting investigators who study pro- and eukaryotic organisms and in focussing on mechanisms by which RNAs interact with the decay apparatus and the factors which modulate decay. The first third of the conference will explore the latest developments in our understanding of how the enzymes of mRNA decay initially interact with their targets. Such interactions largely occur at the ends of RNAs, often involving highly conserved proteins or protein complexes, but with many surprising twists. We anticipate that much needed structural investigations of these interactions will come to fruition and be presented for the first time at the proposed conference. The second portion of the conference will focus on the complex interactions among nascent mRNAs, the degradative machinery, nuclear export, quality control and translation. Understanding these processes and their interplay has myriad implications for regulation of growth, development, and disease. The final portion of the conference will focus on mechanisms of RNA interference (as opposed to the phenomenology) and the application of global approaches to understanding mRNA decay and its impact on whole cells. The conference will provide a superb overview of the latest progress in an exciting field and will propel the next stage of its development.