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RNA 解旋酶 Dhh1p 通过其非保守的 C 末端结构域与 Rbp1p 合作,促进孔蛋白 mRNA 的降解。

The RNA helicase Dhh1p cooperates with Rbp1p to promote porin mRNA decay via its non-conserved C-terminal domain.

机构信息

Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.

出版信息

Nucleic Acids Res. 2012 Feb;40(3):1331-44. doi: 10.1093/nar/gkr803. Epub 2011 Oct 13.

Abstract

The yeast RNA helicase Dhh1p has been shown to associate with components of mRNA decay and is involved in mRNA decapping and degradation. An RNA-binding protein, Rbp1p, is known to bind to the 3'-UTR of porin (POR1) mRNA, and induces mRNA decay by an uncharacterized mechanism. Here, we show that Dhh1p can associate with POR1 mRNA and specifically promote POR1 mRNA decay via its interaction with Rbp1p. As compared to its mammalian homolog RCK/p54/DDX6, Dhh1p has a unique and long extension at its C-terminus. Interestingly, this non-conserved C-terminal region of Dhh1p is required for interaction with Rbp1p and modulating Rbp1p-mediated POR1 mRNA decay. Notably, expression of a C-terminal 81-residue deleted Dhh1p can fully complement the growth defect of a dhh1Δ strain and retains its function in regulating the mRNA level of an RNA-binding protein Edc1p. Moreover, mammalian DDX6 became capable of interacting with Rbp1p and could confer Rbp1p-mediated POR1 mRNA decay in the dhh1Δ strain upon fusion to the C-terminal unique region of Dhh1p. Thus, we propose that the non-conserved C-terminus of Dhh1p plays a role in defining specific interactions with mRNA regulatory factors that promote distinct mRNA decay.

摘要

酵母 RNA 解旋酶 Dhh1p 已被证明与 mRNA 降解的成分相关,并参与 mRNA 脱帽和降解。已知 RNA 结合蛋白 Rbp1p 与孔蛋白(POR1)mRNA 的 3'-UTR 结合,并通过尚未确定的机制诱导 mRNA 降解。在这里,我们表明 Dhh1p 可以与 POR1 mRNA 结合,并通过与 Rbp1p 的相互作用特异性促进 POR1 mRNA 降解。与哺乳动物同源物 RCK/p54/DDX6 相比,Dhh1p 在其 C 末端具有独特且长的延伸。有趣的是,Dhh1p 的这种非保守 C 末端区域对于与 Rbp1p 相互作用和调节 Rbp1p 介导的 POR1 mRNA 降解是必需的。值得注意的是,表达 C 末端缺失 81 个残基的 Dhh1p 可以完全弥补 dhh1Δ 菌株的生长缺陷,并保留其在调节 RNA 结合蛋白 Edc1p 的 mRNA 水平中的功能。此外,哺乳动物 DDX6 能够与 Rbp1p 相互作用,并在融合到 Dhh1p 的 C 末端独特区域后赋予 Rbp1p 介导的 POR1 mRNA 降解能力。因此,我们提出 Dhh1p 的非保守 C 末端在与促进特定 mRNA 降解的 mRNA 调节因子的特异性相互作用中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6acd/3273804/abda09a57fba/gkr803f1.jpg

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