tRNA-m1A modification safeguards fetal liver HSPCs from DNA damage by maintaining iron homeostasis
Year: 2026
Type: article
Abstract: ABSTRACT: Hematopoietic stem and progenitor cell (HSPC) development requires finely tuned gene expression programs, yet the role of transfer RNA (tRNA) modifications in this process remains largely unknown. In this study, we uncover the essential function of the tRNA methyltransferase, Trmt61a, in sustaining fetal liver HSPCs through N1-methyladenosine (m1A) deposition. Ribosome profiling revealed globally declined translation efficiency because of translational blockage upon Trmt61a loss in HSPCs, notably of the transferrin receptor (Tfrc). Mechanistically, m1A reduction caused ribosomal stalling at arginine-CGG codons within Tfrc messenger RNA, thereby suppressing Tfrc synthesis and leading to intracellular iron depletion. This iron deficiency triggered DNA damage and compromised HSPC survival. Our work elucidates an epitranscriptomic pathway, the Trmt61a-m1A-Tfrc axis, that safeguards HSPC integrity by linking tRNA modification to iron homeostasis and preventing DNA damage, providing mechanistic and therapeutic insights into hematopoietic disorders.
Source: Blood
Authors: Yining Liu, Yichen Ma, Panfeng Li, Yongjie Li, Guixian Liang, Xiaoting Zhang, Baofeng Huang, Jinying Peng, Dongyuan Ma, Lu Wang, Ang Li, Chengqi Yi, Feng Liu
Institutions: Chinese Academy of Sciences, University of Chinese Academy of Sciences, Institute of Zoology, Beijing Institute for Stem Cell and Regenerative Medicine, Peking University, Center for Life Sciences, Shandong University, Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Hematology & Blood Diseases Hospital
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,500
OpenAlex ID: W7154173516