tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis

Liu, Yongbo; Zhou, Jing; Li, Xiaoyü; Zhang, Xiaoting; Shi, Jintong; Wang, Xuefei; Li, Hao; Miao, Song; Chen, Huifang; He, Xiaoxiao; Dong, Liting; Lee, Gap Ryol; Zheng, Junke; Liu, Ru-Juan; Su, Bing; Ye, Youqiong; Flavell, Richard A.; Yi, Chengqi; Wu, Yuzhang; Li, Hua Bing

doi:10.1038/s41590-022-01301-3

Cited by 68 publications

(50 citation statements)

References 53 publications

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“…Excitingly, recent work demonstrates that the host immune system also relies on tRNA modifications. A specific tRNA methylation (m1A58) selectively enhances protein translation in a codon-usage manner of a set of proteins that ultimately drive T cell proliferation (29). Together, these findings represent the starting study point of a previously unappreciated tRNA epitranscriptome-virus-immune system regulatory network that is awaiting to be deciphered and will provide novel opportunities for therapeutic interventions.…”

Section: Conclusion and Remarksmentioning

confidence: 88%

The host tRNA epitranscriptome: A new player in RNA virus infections

2022

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Viruses completely depend on the host translation machineries to express the viral proteins. Recent data reveal an unprecedented interaction of positive strand RNA ((+)RNA) viruses with the host tRNA epitranscriptome to favor viral protein expression via a specific reprogramming of codon optimality that ultimately favors decoding of the viral codons. We propose that this feature is shared by multiple RNA viruses and that the involved tRNA modifying enzymes represent promising novel targets for the development of broad-spectrum antivirals.

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Section: Conclusion and Remarksmentioning

confidence: 88%

The host tRNA epitranscriptome: A new player in RNA virus infections

2022

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“…6). Since Rv0208c is a homolog of TrmB, which synthesizes m 7 G at position 46 in E. coli, multiple Mtb tRNA species likely contain m 7 G at position 46 (Fig. 6 and Supplementary Fig.…”

Section: Fig 2 Heat Map Of Misincorporation and Early Termination Fre...mentioning

confidence: 99%

“…The fidelity of base paring between mRNA codons and tRNA anticodons is monitored within ribosomes and is critical for properly incorporating the amino acids bound to the 3' ends of tRNAs into growing polypeptides. For optimal translation, the abundances, and properties of tRNA isoacceptors are fine-tuned by diverse mechanisms, including chemical modifications [1][2][3][4] Dysregulation of tRNA abundance and/or structure leads to defective decoding and results in ribosome pausing and collisions, protein misfolding, stress responses and can have detrimental or lethal effects on the cell [5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

A tRNA modification inMycobacterium tuberculosisfacilitates optimal intracellular growth

Tomasi

Kimura

Rubín

et al. 2023

Preprint

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Diverse chemical modifications fine-tune the function and metabolism of tRNA. Although tRNA modification is universal in all kingdoms of life, profiles of modifications, their functions, and physiological roles have not been elucidated in most organisms including the human pathogen,Mycobacterium tuberculosis(Mtb), the causative agent of tuberculosis. To identify physiologically important modifications, we surveyed the tRNA ofMtb, using tRNA sequencing (tRNA-seq) and genome-mining. Homology searches identified 18 candidate tRNA modifying enzymes that are predicted to create 13 tRNA modifications across all tRNA species. Reverse transcription-derived error signatures in tRNA-seq predicted the sites and presence of 9 modifications. Several chemical treatments prior to tRNA-seq expanded the number of predictable modifications. Deletion ofMtbgenes encoding two modifying enzymes, TruB and MnmA, eliminated their respective tRNA modifications, validating the presence of modified sites in tRNA species. Furthermore, the absence ofmnmAattenuatedMtbgrowth in macrophages, suggesting that MnmA-dependent tRNA uridine sulfation contributes toMtbintracellular growth. Our results lay the foundation for unveiling the roles of tRNA modifications inMtbpathogenesis and developing new therapeutics against tuberculosis.

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“…1 ). 1 Researches in the past few years have led to significant progress toward understanding the mechanism of T-cell activation upon antigen stimulation, 2 which has been extensively learned on the transcriptional level. However, little is known about how other phases of protein translation, especially tRNA-mediated translation, affect T-cell responses.…”

mentioning

confidence: 99%

“…In a recent paper published in Nature Immunology, Liu et al described that the "writers" TRMT6/TRMT61A complex mediated transfer RNA (tRNA) m 1 A modification, facilitating competent translation of certain proteins fundamental to T-cell proliferation in an instant upon activation, 1 demonstrating that tRNA m 1 A methylation as a crucial translational checkpoint paves the way for novel immunotherapies to treat T-cell-related inflammation or cancer via manipulating the m 1 A machinery.…”

mentioning

confidence: 99%

RNA methylation into m1A era: a new regulation over T-cell function

Lin

2023

Sig Transduct Target Ther

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tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis

Cited by 68 publications

References 53 publications

The host tRNA epitranscriptome: A new player in RNA virus infections

The host tRNA epitranscriptome: A new player in RNA virus infections

A tRNA modification inMycobacterium tuberculosisfacilitates optimal intracellular growth

RNA methylation into m1A era: a new regulation over T-cell function

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