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

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 tRNA<sup>Gly(GCC)</sup> to produce 5'-tRHs (5'-tRH-Gly<sup>GCC</sup>) with highly selective target discrimination upon endoplasmic reticulum (ER) stress. Levels of 5'-tRH-Gly<sup>GCC</sup> 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-Gly<sup>GCC</sup>. In addition, under ER stress in vivo, we observe simultaneous induction of IRE1α and 5'-tRH-Gly<sup>GCC</sup> 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-Gly<sup>GCC</sup> in cellular adaptation upon ER stress.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2024-10-28
DOI
https://doi.org/10.1038/s41467-024-53624-4
Citations
14
Primary Topic
RNA regulation and disease
Type
article
Field-Weighted Citation Impact
3.27

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Yoonsoo Hahn, Jeehyeon Bae, Eunkyoung Shin, Hak Kyun Kim et al.
14 citations
Nature Communications
RNA regulation and disease
3.27
article

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

Yoonsoo Hahn, Jeehyeon Bae, Eunkyoung Shin, Hak Kyun Kim, Keun Pil Kim, Hong-Man Kim, Hanyong Jin, Yong‐Hak Kim, Jeongkyu Kim, Minkyung Ryu, Minju Joo, Hye‐Jeong Ha, Haifeng Liu, Daeyoung Kim, Kangseok Lee, Ji‐Hyun Yeom
article en
14 citations

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 tRNA<sup>Gly(GCC)</sup> to produce 5'-tRHs (5'-tRH-Gly<sup>GCC</sup>) with highly selective target discrimination upon endoplasmic reticulum (ER) stress. Levels of 5'-tRH-Gly<sup>GCC</sup> 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-Gly<sup>GCC</sup>. In addition, under ER stress in vivo, we observe simultaneous induction of IRE1α and 5'-tRH-Gly<sup>GCC</sup> 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-Gly<sup>GCC</sup> in cellular adaptation upon ER stress.

Nature CommunicationsVol. 15(1)
Yanbian University (CN), Daegu Catholic University (KR), Czech Academy of Sciences, Institute of Biotechnology (CZ), Chung-Ang University (KR)
Chungnam National University, Yonsei University, Ministry of Health and Welfare, National Research Foundation of Korea
Openalex Percentile: Top 7%
RNA regulation and disease
3.27
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.