Emerging regulatory roles for tRNA fragments

tRNA 片段的新兴调控作用

• 批准号: RGPIN-2017-05516
• 负责人: Masse, Eric
• 金额: $ 2.91万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=658975
• 关键词: Emerging; regulatory; roles; tRNA; fragments

TITLE: Emerging regulatory roles for tRNA fragments******Transfer RNAs (tRNAs) are mostly considered to be amino acid carriers that decode information contained in the nucleotide sequence of messenger RNAs (mRNA) into specific polypeptide sequences. Beside playing a crucial role in protein synthesis, tRNAs are also involved in various biological processes including stress response, gene regulation and plasmid replication. tRNAs are transcribed as pre-tRNA transcripts and are processed by ribonucleases and diverse modification enzymes to release mature tRNAs as well as tRNA-derived fragments (tRFs). Long considered as “junk” RNAs, tRNA-derived fragments (tRFs) recently turned out to be important functional elements of eukaryotic and prokaryotic cells. With the help of high-throughput sequencing and genome-wide analysis, recent reports have described surprising functions for these molecules. Although roles of most identified tRNA fragments are still elusive, latest discoveries demonstrate that they could use similar mechanisms than well-characterized small regulatory RNAs (gene silencing, protein sequestration, sRNA buffering). Taking into consideration the latest findings in this field, it appears clear that tRNAs represent an impressive source of various functional RNAs. My laboratory successfully described the first functional tRF in prokaryotes. Inspired by recent results, my students have performed a global screen for new tRFs in the model organism Escherichia coli. We found many potential candidates that will be the focus of this proposal. One of these tRFs seems to regulate global translation initiation, which could dramatically impact our view of gene expression. Another tRF of interest might regulate the expression of particular mRNAs involved in antibiotics resistance. We also observed that at least one RNA-binding protein can affect the processing of tRNAs, which also suggests for the first time that tRF biogenesis can be modulated by the cell. We will explore the biogenesis and function of these exciting molecules where they were shown to play important roles. Understanding how tRFs interact with other RNAs will help understanding a totally new mechanism of gene expression. We believe that tRFs might help the coordination of translation machinery and the expression of gene controlling the cellular metabolism, a mechanism that has never been described previously.

TRNA片段的新的调节作用转移RNA(TRNAs)通常被认为是氨基酸载体，它将信使RNAs(MRNAs)的核苷酸序列中包含的信息解码为特定的多肽序列。除了在蛋白质合成中发挥重要作用外，tRNAs还参与应激反应、基因调控和质粒复制等多种生物学过程。TRNA被转录为前tRNA转录本，由核糖核酸酶和各种修饰酶处理，释放成熟的tRNA和tRNA衍生片段(TRFs)。TRNA衍生片段(TRFs)长期以来被认为是“垃圾”RNA，近年来被证明是真核细胞和原核细胞的重要功能元件。在高通量测序和全基因组分析的帮助下，最近的报告描述了这些分子令人惊讶的功能。尽管大多数已识别的tRNA片段的作用仍然难以捉摸，但最新的发现表明，它们可以使用与特征良好的小调节RNA相似的机制(基因沉默、蛋白质隔离、sRNA缓冲)。考虑到该领域的最新发现，似乎很明显，tRNAs代表了各种功能RNAs的令人印象深刻的来源。我的实验室成功地在原核生物中成功地描述了第一个具有功能的转录因子。受到最近的研究结果的启发，我的学生们在全球范围内对模式生物大肠杆菌中的新TRFs进行了筛选。我们发现了许多潜在的候选人，这些候选人将是这项提案的重点。这些转录因子中的一个似乎调节着全球翻译的启动，这可能会极大地影响我们对基因表达的看法。另一个令人感兴趣的TRF可能调节参与抗生素耐药性的特定mRNAs的表达。我们还观察到至少有一种RNA结合蛋白可以影响tRNAs的处理，这也首次表明TRF的生物发生可以由细胞调控。我们将探索这些令人兴奋的分子的生物发生和功能，在那里它们被证明扮演着重要的角色。了解TRFs如何与其他RNAs相互作用将有助于理解一种全新的基因表达机制。我们认为，TRFs可能有助于协调翻译机制和控制细胞代谢的基因的表达，这是以前从未描述过的机制。