期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 21, 页码 -出版社
MDPI
DOI: 10.3390/ijms232113100
关键词
tRNA; RTCB ligase complex; oxidative stress; tiRNAs; angiogenin
资金
- National Institutes of Health [R01 GM126150, R01 GM146997]
- Japan Society for the Promotion of Science [21K06865, 19H03509]
- Japan Agency for Medical Research and Development (AMED) [JP22zf0127001]
Under stress conditions, transfer RNAs (tRNAs) are cleaved to produce tiRNAs, which are negatively regulated by the RTCB ligase complex. RTCB-LC can repair tiRNAs to full-length tRNAs in vitro. Hydrogen peroxide enhances tiRNA production under stress conditions by inhibiting RTCB-LC.
Under stress conditions, transfer RNAs (tRNAs) are cleaved by stress-responsive RNases such as angiogenin, generating tRNA-derived RNAs called tiRNAs. As tiRNAs contribute to cytoprotection through inhibition of translation and prevention of apoptosis, the regulation of tiRNA production is critical for cellular stress response. Here, we show that RTCB ligase complex (RTCB-LC), an RNA ligase complex involved in endoplasmic reticulum (ER) stress response and precursor tRNA splicing, negatively regulates stress-induced tiRNA production. Knockdown of RTCB significantly increased stress-induced tiRNA production, suggesting that RTCB-LC negatively regulates tiRNA production. Gel-purified tiRNAs were repaired to full-length tRNAs by RtcB in vitro, suggesting that RTCB-LC can generate full length tRNAs from tiRNAs. As RTCB-LC is inhibited under oxidative stress, we further investigated whether tiRNA production is promoted through the inhibition of RTCB-LC under oxidative stress. Although hydrogen peroxide (H2O2) itself did not induce tiRNA production, it rapidly boosted tiRNA production under the condition where stress-responsive RNases are activated. We propose a model of stress-induced tiRNA production consisting of two factors, a trigger and booster. This RTCB-LC-mediated boosting mechanism may contribute to the effective stress response in the cell.
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