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不同小鼠组织中 tRNA 转录组和翻译组的动态景观。

Dynamic Landscapes of tRNA Transcriptomes and Translatomes in Diverse Mouse Tissues.

机构信息

Center for Translational Medicine, Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510080, China.

Department of Medical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Center for Stem Cell Biology and Tissue Engineering, MOE Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-sen University, Guangzhou 510080, China.

出版信息

Genomics Proteomics Bioinformatics. 2023 Aug;21(4):834-849. doi: 10.1016/j.gpb.2022.07.006. Epub 2022 Aug 8.

Abstract

Although the function of tRNAs in the translational process is well established, it remains controversial whether tRNA abundance is tightly associated with translational efficiency (TE) in mammals. Moreover, how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed. Here, we measured both tRNA expression using demethylase-tRNA sequencing (DM-tRNA-seq) and TE of mRNAs using ribosome-tagging sequencing (RiboTag-seq) in the brain, heart, and testis of mice. Remarkable variation in the expression of tRNA isodecoders was observed among different tissues. When the statistical effect of isodecoder-grouping on reducing variations is considered through permutating the anticodons, we observed an expected reduction in the variation of anticodon expression across all samples, an unexpected smaller variation of anticodon usage bias, and an unexpected larger variation of tRNA isotype expression at amino acid level. Regardless of whether or not they share the same anticodons, the isodecoders encoding the same amino acids are co-expressed across different tissues. Based on the expression of tRNAs and the TE of mRNAs, we find that the tRNA adaptation index (tAI) and TE are significantly correlated in the same tissues but not between tissues; and tRNA expression and the amino acid composition of translating peptides are positively correlated in the same tissues but not between tissues. We therefore hypothesize that the tissue-specific expression of tRNAs might be due to post-transcriptional mechanisms. This study provides a resource for tRNA and translation studies, as well as novel insights into the dynamics of tRNAs and their roles in translational regulation.

摘要

尽管 tRNA 在翻译过程中的功能已经得到很好的证实,但 tRNA 丰度是否与哺乳动物的翻译效率(TE)紧密相关仍然存在争议。此外,tRNA 的表达对哺乳动物组织特异性蛋白质组的建立有多么关键,尚未得到很好的解决。在这里,我们使用脱甲基酶 tRNA 测序(DM-tRNA-seq)测量了小鼠大脑、心脏和睾丸中 tRNA 的表达,并用核糖体标记测序(RiboTag-seq)测量了 mRNA 的 TE。在不同组织中观察到 tRNA 同功密码子的表达存在显著差异。当通过置换反密码子考虑同功密码子分组对减少变异的统计效果时,我们观察到所有样本中反密码子表达的变异预期减少,密码子使用偏好的变异意外变小,以及氨基酸水平上 tRNA 同工型表达的变异意外变大。无论它们是否共享相同的反密码子,编码相同氨基酸的同功密码子在不同组织中都是共表达的。基于 tRNA 的表达和 mRNA 的 TE,我们发现 tRNA 适应指数(tAI)和 TE 在相同组织中显著相关,但在不同组织之间不相关;并且 tRNA 表达与翻译肽的氨基酸组成在相同组织中呈正相关,但在不同组织之间不相关。因此,我们假设 tRNA 在组织中的特异性表达可能是由于转录后机制。本研究为 tRNA 和翻译研究提供了资源,并为 tRNA 及其在翻译调控中的作用的动态提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/10787195/93fde79f0962/gr1.jpg

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