5′-tRNAGly(GCC) halves generated by IRE1α are linked to the ER stress response

Hanyong Jin, Ji-Hyun Yeom, Eunkyoung Shin, Yoonjie Ha, Haifeng Liu, Daeyoung Kim, Minju Joo, Yong-Hak Kim, Hak Kyun Kim, Minkyung Ryu, Hong-Man Kim, Jeongkyu Kim, Keun P. Kim, Yoonsoo Hahn, Jeehyeon Bae () and Kangseok Lee ()
Additional contact information
Hanyong Jin: Yanbian University
Ji-Hyun Yeom: Chung-Ang University
Eunkyoung Shin: Chung-Ang University
Yoonjie Ha: Chung-Ang University
Haifeng Liu: Chung-Ang University
Daeyoung Kim: Chung-Ang University
Minju Joo: Chung-Ang University
Yong-Hak Kim: Catholic University of Daegu
Hak Kyun Kim: Chung-Ang University
Minkyung Ryu: Chung-Ang University
Hong-Man Kim: NES Biotechnology
Jeongkyu Kim: Chung-Ang University
Keun P. Kim: Chung-Ang University
Yoonsoo Hahn: Chung-Ang University
Jeehyeon Bae: Chung-Ang University
Kangseok Lee: Chung-Ang University

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Transfer RNA 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. Levels of 5′-tRH-GlyGCC positively affect cancer cell proliferation and modulate mRNA isoform biogenesis both in vitro and in vivo; these effects require co-expression of two nuclear ribonucleoproteins, HNRNPM and HNRNPH2, which we identify as binding proteins of 5′-tRH-GlyGCC. In addition, under ER stress in vivo, we observe 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.

Date: 2024
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DOI: 10.1038/s41467-024-53624-4

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