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The TUTase URT1 connects decapping activators and prevents the accumulation of excessively deadenylated mRNAs to avoid siRNA biogenesis
bioRxiv - Molecular Biology Pub Date : 2020-12-15 , DOI: 10.1101/2020.05.26.114322
Hélène Scheer , Caroline de Almeida , Emilie Ferrier , Quentin Simonnot , Laure Poirier , David Pflieger , François M. Sement , Sandrine Koechler , Christina Piermaria , Paweł Krawczyk , Seweryn Mroczek , Johana Chicher , Lauriane Kuhn , Andrzej Dziembowski , Philippe Hammann , Hélène Zuber , Dominique Gagliardi

Uridylation is a widespread modification destabilizing eukaryotic mRNAs. Yet, molecular mechanisms underlying TUTase-mediated mRNA degradation remain mostly unresolved. Here, we report that the Arabidopsis TUTase URT1 participates in a molecular network connecting several translational repressors/decapping activators. URT1 directly interacts with DECAPPING 5 (DCP5), the Arabidopsis ortholog of human LSM14 and yeast Scd6, and this interaction connects URT1 to additional decay factors like DDX6/Dhh1-like RNA helicases. Nanopore direct RNA sequencing reveals a global role of URT1 in shaping poly(A) tail length, notably by preventing the accumulation of excessively deadenylated mRNAs. Based on in vitro and in planta data, we propose a model that explains how URT1 could reduce the accumulation of oligo(A)-tailed mRNAs both by favoring their degradation and because 3′ terminal uridines intrinsically hinder deadenylation. Importantly, preventing the accumulation of excessively deadenylated mRNAs avoids the biogenesis of illegitimate siRNAs that silence endogenous mRNAs and perturb Arabidopsis growth and development.

中文翻译:

TUTase URT1连接去盖激活因子并防止过多的去甲腺苷酸化的mRNA积累,以避免siRNA生物发生

铀酰化是破坏真核mRNA的广泛修饰。但是,TUTase介导的mRNA降解的分子机制仍未解决。在这里,我们报告拟南芥TUTase URT1参与了一个分子网络,该分子网络连接了几个翻译阻遏物/去盖活化剂。URT1直接与DECAPPING 5(DCP5),人LSM14的拟南芥直系同源基因和酵母Scd6相互作用,这种相互作用将URT1连接到其他衰变因子,如DDX6 / Dhh1样RNA解旋酶。纳米孔直接RNA测序揭示了URT1在塑造poly(A)尾巴长度中的全局作用,特别是通过防止过度去甲腺苷酸化的mRNA的积累。根据体外和植物数据,我们提出了一个模型,解释了URT1如何通过促进寡核苷酸(A)尾部的mRNA降解以及3'末端尿苷固有地阻碍腺苷酸化来减少其积累。重要的是,防止过度去腺苷酸化的mRNA的积累可避免使内源性mRNA沉默并干扰拟南芥的生长和发育的非法siRNA的生物发生。
更新日期:2020-12-15
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