{"id":418,"title":"LENG8 granule regulates alternative polyadenylation in mammals","title_zh":"LENG8颗粒调控哺乳动物可变多聚腺苷酸化","url":"https://pubmed.ncbi.nlm.nih.gov/42881150","doi":"10.1038/s41467-026-77634-6","pmid":"42881150","journal":"Nat Commun","kind":"paper","lang":"en","published_at":"2026-09-15T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Wu Z","Du C","Li Y","Huang X","Qin Y","Zhong A","Rao M","Liu F","Zhu H","Zhou Y","Dai P"],"primary_topic":"repro-genetics","topics":[{"slug":"ethics-policy","score":2.0,"hits":["regulation","regulatory"]},{"slug":"ivg-stem","score":1.0,"hits":["germ cells"]}],"topic_score":2.0,"preference_score":0.0,"preference_labels":[],"llm_score":78.0,"final_score":86.0,"score_dims":{"novelty":88,"rigor":85,"impact":72,"relevance":52,"translation":40},"recommend_reason":"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。","keywords":["LENG8颗粒","可变多聚腺苷酸化","相分离","3'UTR","m6A","雄性生殖细胞"],"selected":1,"story_id":439,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"nat-commun","journal_tier":"cns-sub","journal_if":14.7,"is_mock":false,"summary_zh":"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。","summary":"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.","interpretation_basis":null,"fulltext_status":"non_oa","interpretation":null,"fulltext":{"available":false,"status":"non_oa","reason":"Europe PMC 未收录免费全文（非 OA，或该来源不在 Europe PMC 全文范围内，如 bioRxiv 预印本）：isOpenAccess=False, inEPMC=False","pmcid":null,"license":null,"chars":0,"source":"Europe PMC","fetched_at":"2026-11-08T04:19:25+00:00"}}