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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711679
• 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.

标题：tRNA 片段的新兴调控作用 转移RNA（tRNA）通常被认为是氨基酸载体，其将信使RNA（mRNA）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关键作用外，tRNA 还参与各种生物过程，包括应激反应、基因调控和质粒复制。 tRNA 被转录为前 tRNA 转录物，并由核糖核酸酶和多种修饰酶加工，释放成熟的 tRNA 以及 tRNA 衍生片段 (tRF)。 tRNA 衍生片段 (tRF) 长期以来被认为是“垃圾”RNA，但最近被证明是真核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，它们可以使用与已充分表征的小调节 RNA 类似的机制（基因沉默、蛋白质隔离、sRNA 缓冲）。考虑到该领域的最新发现，很明显 tRNA 代表了各种功能性 RNA 的令人印象深刻的来源。我的实验室成功地描述了原核生物中的第一个功能性 tRF。受最近结果的启发，我的学生在模式生物大肠杆菌中对新的 tRF 进行了全球筛选。我们发现许多潜在的候选人将成为该提案的重点。其中一个 tRF 似乎调节全局翻译起始，这可能会极大地影响我们对基因表达的看法。另一个感兴趣的 tRF 可能调节与抗生素耐药性相关的特定 mRNA 的表达。我们还观察到至少一种RNA结合蛋白可以影响tRNA的加工，这也首次表明tRF生物发生可以由细胞调节。我们将探索这些令人兴奋的分子的生物发生和功能，它们被证明发挥着重要作用。了解 tRF 如何与其他 RNA 相互作用将有助于理解全新的基因表达机制。我们相信 tRF 可能有助于协调翻译机制和控制细胞代谢的基因表达，这是一种以前从未描述过的机制。