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LENG8颗粒调控哺乳动物可变多聚腺苷酸化

LENG8 granule regulates alternative polyadenylation in mammals

PubMed · CNS/大子刊/四大医学刊(生殖相关) · Nat Commun 大子刊 IF 14.7 · 文献 · 2026-09-15
Wu Z, Du C, Li Y, Huang X, Qin Y, Zhong A, Rao M, Liu F, Zhu H, Zhou Y 等 11 人
DOI 10.1038/s41467-026-77634-6 · PMID 42881150 · 原文链接 ↗ · Scholar
综合 86.0 模型 78.0 · deepseek/deepseek-flash · 强度 low 已入选 期刊加权 +8 伦理、法规与指南 生殖干细胞与体外配子发生
新颖 88严谨 85影响 72领域相关 52转化 40

摘要

该研究揭示哺乳动物细胞核内存在一种无膜细胞器——LENG8颗粒(G颗粒),并证明其是可变多聚腺苷酸化(APA)调控的活跃枢纽。LENG8缺失会导致培养细胞及雄性生殖细胞中广泛的3'UTR延长。机制上,相分离驱动的LENG8颗粒形成促进LENG8与CPSF4互作,并推动切割与多聚腺苷酸化复合物组装,从而偏好使用近端poly(A)位点;YTHDC1-m⁶A景观参与调控颗粒形成、维持及靶标选择。LENG8颗粒还与核斑点存在空间定位和功能互作,其靶转录本3'UTR长度与颗粒组装特征呈细胞类型和发育阶段依赖性。

原文摘要

Membraneless organelles (MLOs) participate in multiple cellular processes and layers of gene regulation. Alternative polyadenylation (APA) represents a pervasive gene regulatory mechanism that generates distinct 3' untranslated regions (UTRs) in transcripts. However, whether specific MLOs exist in mammals to regulate APA remains largely unknown. Here, we unveil a nuclear body, termed the LENG8 granule (G granule), that functions as an active hub for APA regulation. LENG8 deletion induces extensive 3'UTR lengthening in both cultured cells and male germ cells. Mechanistically, phase separation-driven LENG8 granule formation facilitates LENG8-CPSF4 interaction and promotes the subsequent assembly of the cleavage and polyadenylation (CPA) complex, thereby favoring proximal poly(A) site usage in target transcripts. We further elucidate that YTHDC1-m⁶A landscapes orchestrate LENG8 granule formation/maintenance and target selection. Moreover, LENG8 granules exhibit spatial localization and functional crosstalk with nuclear speckles. Notably, the 3'UTR length of target transcripts correlates with LENG8 granule assembly and properties in a cell-type- and developmental stage-dependent manner. Our study establishes LENG8 as a critical regulator of mRNA 3' end processing and demonstrates that LENG8 granules modulate mammalian APA, advancing our understanding of MLOs-mediated poly(A) site selection.

推荐理由:机制新颖,首次将LENG8颗粒、相分离与哺乳动物APA调控及雄性生殖细胞3'UTR延长联系起来,对生殖遗传和RNA调控研究有启示;但距离ART临床决策与实验室转化较远,适合相关基础研究者阅读。

关键词:LENG8颗粒 · 可变多聚腺苷酸化 · 相分离 · 3'UTR · m6A · 雄性生殖细胞

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所属事件:LENG8颗粒调控哺乳动物可变多聚腺苷酸化 热度 0.0 · 0 个来源

条目 #418 · 入库 2026-11-08 11:44 · JSON · Journal Article, Research Support, Non-U.S. Gov't