Work

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

Year: 2026

Type: article

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.

Source: Journal of Molecular Cell Biology

DOI: 10.1093/jmcb/mjag030

Authors: Xixi Ma, Yuliang Huang, Hao Jin, Rui Zhang, Fangzhou Liu, Aifu Lin, Tianhua Zhou, Shanshan Xie

Institutions: Children's Hospital of Zhejiang University, Zhejiang University, University of Toronto

Language: English

Topic: Nuclear Structure and Function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,900

OpenAlex ID: W7203718485

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