Proteomics

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Endoplasmic reticulum stress-induced tRNA fragmentation


ABSTRACT: Transfer RNA-derived fragments have specific biological roles. However, it is still not characterized what factors are responsible for generation of 5′-tRHs in certain conditions, such as metabolic disease and maturation of reproductive cells. Here, we report that Inositol-requiring enzyme 1α (IRE1α), a major ER stress sensor protein, cleaves specifically anticodon stem-loop region of tRNAGly(GCC) and produces 5′-tRHs. Using an RNA-seq-based approach, we identified cleavage sites in tRNAGly(GCC), generating 5′-tRHs in KGN cells (human ovarian granulosa cells) in an IRE1α-expression dependent manner. In vitro cleavage analyses further supported that IRE1α generates 5′-tRHs from tRNAGly(GCC) (5′-tRH-GlyGCC) with highly selective target discrimination. The production of 5′-tRH-GlyGCC was promoted upon endoplasmic reticulum (ER) stress, which induced IRE1α expression, in KGN cells as well as other cancer cell lines such as HeLa and HepG. In addition, transfection of synthetic 5′-tRH-GlyGCC mimics promoted survival of KGN and HeLa cells; this effect required expression of HNRNPM and HNRNPH2, which were identified as binding proteins of 5′-tRH-GlyGCC.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Granulosa Cell

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Yong-Hak Kim  

LAB HEAD: Kim, Yong-Hak

PROVIDER: PXD013798 | Pride | 2024-10-30

REPOSITORIES: pride

Dataset's files

Source:
Action DRS
KH1.msf Msf
KH1.raw Raw
KH10.msf Msf
KH10.raw Raw
KH11.msf Msf
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