| Autor: |
Ji-Hyun Yeom, Eunkyoung Shin, Yoonjie Ha, Minju Joo, Hanyong Jin, Haifeng Liu, Daeyoung Kim, Yong-Hak Kim, Hak Kyun Kim, Jeongkyu Kim, Hong-Man Kim, Minkyung Ryu, Keun Pil Kim, Yoonsoo Hahn, Jeehyeon Bae, Kangseok Lee |
| Rok vydání: |
2022 |
| DOI: |
10.21203/rs.3.rs-1464849/v1 |
| Popis: |
Transfer RNA (tRNA) halves (tRHs) have various biological functions. However, the biogenesis of specific 5′-tRHs under certain conditions remains unknown. Here, we report that inositol-requiring enzyme 1α (IRE1α) cleaves the anticodon stem-loop region of tRNAGly(GCC) to produce 5′-tRHs (5′-tRH-GlyGCC) with highly selective target discrimination upon endoplasmic reticulum (ER) stress. We observed IRE1α expression-dependent 5′-tRH-GlyGCC production in human cancer cells. Levels of 5′-tRH-GlyGCC were positively correlated with the degree of cancer cell proliferation both in vitro and in vivo; this effect required co-expression of two nuclear ribonucleoproteins, HNRNPM and HNRNPH2, which we identified as binding proteins of 5′-tRH-GlyGCC. In addition, 5′-tRH-GlyGCC modulated mRNA isoform biogenesis. Furthermore, under ER stress in vivo, we observed simultaneous induction of IRE1α and 5′-tRH-GlyGCC expression in mouse organs and a distantly related organism, Cryptococcus neoformans. Thus, collectively, our findings indicate an evolutionarily conserved function for IRE1α-generated 5′-tRH-GlyGCC in cellular adaptation upon ER stress. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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