气候变化领域集成服务门户(CCPortal): Dynamic changes in tRNA modifications and abundance during T cell activation

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DOI	10.1073/pnas.2106556118
	Dynamic changes in tRNA modifications and abundance during T cell activation
	Rak R.; Polonsky M.; Eizenberg-Magar I.; Mo Y.; Sakaguchi Y.; Mizrahi O.; Nachshon A.; Reich-Zeliger S.; Stern-Ginossar N.; Dahan O.; Suzuki T.; Friedman N.; Pilpel Y.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:42
英文摘要	The tRNA pool determines the efficiency, throughput, and accuracy of translation. Previous studies have identified dynamic changes in the tRNA (transfer RNA) supply and mRNA (messenger RNA) demand during cancerous proliferation. Yet dynamic changes may also occur during physiologically normal proliferation, and these are less well characterized. We examined the tRNA and mRNA pools of T cells during their vigorous proliferation and differentiation upon triggering their antigen receptor. We observed a global signature of switch in demand for codons at the early proliferation phase of the response, accompanied by corresponding changes in tRNA expression levels. In the later phase, upon differentiation, the response of the tRNA pool relaxed back to the basal level, potentially restraining excessive proliferation. Sequencing of tRNAs allowed us to evaluate their diverse base-modifications. We found that two types of tRNA modifications, wybutosine and ms2t6A, are reduced dramatically during T cell activation. These modifications occur in the anticodon loops of two tRNAs that decode “slippery codons,” which are prone to ribosomal frameshifting. Attenuation of these frameshift-protective modifications is expected to increase the potential for proteome-wide frameshifting during T cell proliferation. Indeed, human cell lines deleted of a wybutosine writer showed increased ribosomal frameshifting, as detected with an HIV gag-pol frameshifting site reporter. These results may explain HIV's specific tropism toward proliferating T cells since it requires ribosomal frameshift exactly on the corresponding codon for infection. The changes in tRNA expression and modifications uncover a layer of translation regulation during T cell proliferation and expose a potential tradeoff between cellular growth and translation fidelity. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	HIV; T cell activation; Transfer RNA; TRNA-modifications
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238775
作者单位	Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel; Institute of Animal Science, Agricultural Research Organization, The Volcani Center, Bet Dagan, 7505101, Israel; Department of Immunology, Weizmann Institute of Science, Rehovot, 76100, Israel; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, United States; Department of Chemistry and Biotechnology, University of Tokyo, Tokyo, 113-8654, Japan
推荐引用方式 GB/T 7714	Rak R.,Polonsky M.,Eizenberg-Magar I.,et al. Dynamic changes in tRNA modifications and abundance during T cell activation[J],2021,118(42).
APA	Rak R..,Polonsky M..,Eizenberg-Magar I..,Mo Y..,Sakaguchi Y..,...&Pilpel Y..(2021).Dynamic changes in tRNA modifications and abundance during T cell activation.Proceedings of the National Academy of Sciences of the United States of America,118(42).
MLA	Rak R.,et al."Dynamic changes in tRNA modifications and abundance during T cell activation".Proceedings of the National Academy of Sciences of the United States of America 118.42(2021).