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A conserved motif in human BTG1 and BTG2 proteins mediates interaction with the poly(A) binding protein PABPC1 to stimulate mRNA deadenylation
RNA Biology ( IF 3.6 ) Pub Date : 2021-06-01 , DOI: 10.1080/15476286.2021.1925476
Hamza Amine 1, 2, 3, 4 , Nina Ripin 5 , Sahil Sharma 6, 7 , Georg Stoecklin 6, 7 , Frédéric H Allain 5, 8 , Bertrand Séraphin 1, 2, 3, 4 , Fabienne Mauxion 1, 2, 3, 4
Affiliation  

ABSTRACT

Antiproliferative BTG/Tob proteins interact directly with the CAF1 deadenylase subunit of the CCR4-NOT complex. This binding requires the presence of two conserved motifs, boxA and boxB, characteristic of the BTG/Tob APRO domain. Consistently, these proteins were shown to stimulate mRNA deadenylation and decay in several instances. Two members of the family, BTG1 and BTG2, were reported further to associate with the protein arginine methyltransferase PRMT1 through a motif, boxC, conserved only in this subset of proteins. We recently demonstrated that BTG1 and BTG2 also contact the first RRM domain of the cytoplasmic poly(A) binding protein PABPC1. To decipher the mode of interaction of BTG1 and BTG2 with partners, we performed nuclear magnetic resonance experiments as well as mutational and biochemical analyses. Our data demonstrate that, in the context of an APRO domain, the boxC motif is necessary and sufficient to allow interaction with PABPC1 but, unexpectedly, that it is not required for BTG2 association with PRMT1. We show further that the presence of a boxC motif in an APRO domain endows it with the ability to stimulate deadenylation in cellulo and in vitro. Overall, our results identify the molecular interface allowing BTG1 and BTG2 to activate deadenylation, a process recently shown to be necessary for maintaining T-cell quiescence.



中文翻译:

人 BTG1 和 BTG2 蛋白中的一个保守基序介导与 poly(A) 结合蛋白 PABPC1 的相互作用以刺激 mRNA 去腺苷酸化

摘要

抗增殖 BTG/Tob 蛋白直接与 CCR4-NOT 复合物的 CAF1 去腺苷酶亚基相互作用。这种结合需要存在两个保守的基序 boxA 和 boxB,这是 BTG/Tob APRO 结构域的特征。一致地,这些蛋白质在几种情况下被证明可以刺激 mRNA 去腺苷酸化和衰变。据报道,该家族的两个成员 BTG1 和 BTG2 通过仅在该蛋白质子集中保守的基序 boxC 与蛋白质精氨酸甲基转移酶 PRMT1 相关联。我们最近证明 BTG1 和 BTG2 也接触细胞质 p​​oly(A) 结合蛋白 PABPC1 的第一个 RRM 域。为了破译 BTG1 和 BTG2 与合作伙伴的相互作用模式,我们进行了核磁共振实验以及突变和生化分析。我们的数据表明,在 APRO 域的上下文中,boxC 基序对于允许与 PABPC1 交互是必要且足够的,但出乎意料的是,BTG2 与 PRMT1 的关联不需要它。我们进一步表明,APRO 结构域中 boxC 基序的存在赋予它刺激去腺苷酸化的能力在纤维素体外。总体而言,我们的结果确定了允许 BTG1 和 BTG2 激活去腺苷酸化的分子界面,最近证明这一过程对于维持 T 细胞静止是必要的。

更新日期:2021-06-01
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