ALKBH3 is an NPM1-dependent nucleolar protein required for rRNA biogenesis and translation

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ID: 325589
2026
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Abstract
The nucleolus is a membraneless nuclear organelle formed by liquid-liquid phase separation and serves as the hub for ribosomal RNA (rRNA) transcription and ribosome assembly. Here, we identify ALKBH3, a Fe(II)/α-ketoglutarate-dependent dioxygenase, as a previously unrecognized nucleolar protein that colocalizes with the scaffold protein Nucleophosmin 1 (NPM1). Loss of ALKBH3 reduced nascent and precursor rRNA levels, impaired global protein translation, and suppressed cell proliferation. Although ALKBH3 lacked intrinsic LLPS capacity, it was recruited into NPM1 condensates via a direct interaction mediated by an N-terminal KRRRAR motif. Consistently, NPM1 knockdown diminished ALKBH3 nucleolar localization in cells, while in vitro assays demonstrated ALKBH3-NPM1 co-condensation. In zebrafish, alkbh3 knockdown decreased pre-rRNA abundance and caused dose-dependent developmental delays. Together, these findings establish ALKBH3 as an NPM1-dependent nucleolar client protein critical for rRNA biogenesis, protein synthesis, and vertebrate development.
Reference Key
openalex_W7203718485 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Xixi Ma, Yuliang Huang, Hao Jin, Rui Zhang, Fangzhou Liu, Aifu Lin, Tianhua Zhou, Shanshan Xie
Journal journal of molecular cell biology
Year 2026
DOI
10.1093/jmcb/mjag030
URL
https://doi.org/10.1093/jmcb/mjag030
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