浙江大学谢珊珊等合作的一项研究发现ALKBH3是一种依赖npm1的核仁蛋白，是rRNA生物发生和翻译所必需的。这一研究成果于2026年8月17日发表在国际顶尖学术期刊《分子细胞生物学报》上。

该研究发现ALKBH3是一种铁(II)/α-酮戊二酸依赖的双加氧酶，是一种以前未被识别的核仁蛋白，它与支架蛋白核磷蛋白1 （NPM1）共定位。ALKBH3的缺失降低了新生和前体rRNA水平，破坏了整体蛋白翻译，抑制了细胞增殖。尽管ALKBH3缺乏内在的LLPS能力，但它通过n端KRRRAR基序介导的直接相互作用被招募到NPM1凝析物中。一致地，NPM1敲除降低了ALKBH3在细胞中的核仁定位，而体外实验显示ALKBH3 - NPM1共凝。在斑马鱼中，ALKBH3敲除降低了前rRNA的丰度，并导致了剂量依赖性的发育迟缓。总之，这些发现证实了ALKBH3是NPM1依赖的核仁蛋白，对rRNA生物发生、蛋白质合成和脊椎动物发育至关重要。

据了解，核糖体是由液-液相分离形成的无膜核细胞器，是核糖体RNA转录和核糖体组装的中枢。

附：英文原文

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

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

Issue&Volume: 2026-08-17

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.

DOI: 10.1093/jmcb/mjag030

Source: https://dx.doi.org/10.1093/jmcb/mjag030