TRNA m1A modification ensures HSPC production via modulating Nrf1 translation in zebrafish

ABSTRACT: During embryogenesis, nascent hematopoietic stem and progenitor cells (HSPCs) arise from hemogenic endothelium via endothelial-to-hematopoietic transition (EHT). While this process is orchestrated by multiple intrinsic factors, the role of tRNA-mediated translational control during EHT remains poorly understood. Here, we identify tRNA m1A58 as a predominant tRNA modification in specifying HSPC fate in zebrafish embryos. Depletion of trmt61a compromises HSPC production in the aorta-gonad-mesonephros (AGM) region, accompanied by attenuated tRNA m1A58 levels and evident p53-dependent apoptosis. Mechanistically, Trmt61a-mediated tRNA m1A58 modification enhances translation efficiency of nuclear respiratory factor 1 (Nrf1), a key regulator of mitochondrial biogenesis. Consequently, trmt61a defi

SUBMITTER: Zhenkun Dong 

PROVIDER: S-SCDT-10_1038-S44319-026-00805-5 | biostudies-other |

REPOSITORIES: biostudies-other