5'-tRNA Halves Generated by IRE1α Are Linked to the ER Stress Response

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Oct 29

PMID 39468069

Authors

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

Kangseok Lee

Affiliations

Soon will be listed here.

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

Citing Articles

The functions and modifications of tRNA-derived small RNAs in cancer biology.

Saad A, Zhang K, Deng Q, Zhou J, Ge L, Wang H Cancer Metastasis Rev. 2025; 44(1):38.

PMID: 40072687 DOI: 10.1007/s10555-025-10254-6.

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