Max Perutz Labs, Vienna Biocenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030 Vienna, Austria.
Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, 1030 Vienna, Austria.
Nucleic Acids Res. 2024 Aug 27;52(15):9076-9091. doi: 10.1093/nar/gkae610.
The MUT-7 family of 3'-5' exoribonucleases is evolutionarily conserved across the animal kingdom and plays essential roles in small RNA production in the germline. Most MUT-7 homologues carry a C-terminal domain of unknown function named MUT7-C appended to the exoribonuclease domain. Our analysis shows that the MUT7-C is evolutionary ancient, as a minimal version of the domain exists as an individual protein in prokaryotes. In animals, MUT7-C has acquired an insertion that diverged during evolution, expanding its functions. Caenorhabditis elegans MUT-7 contains a specific insertion within MUT7-C, which allows binding to MUT-8 and, consequently, MUT-7 recruitment to germ granules. In addition, in C. elegans and human MUT-7, the MUT7-C domain contributes to RNA binding and is thereby crucial for ribonuclease activity. This RNA-binding function most likely represents the ancestral function of the MUT7-C domain. Overall, this study sheds light on MUT7-C and assigns two functions to this previously uncharacterized domain.
MUT-7 家族的 3'-5' 外切核糖核酸酶在动物界中是进化保守的，在生殖系中小 RNA 的产生中发挥着重要作用。大多数 MUT-7 同源物带有一个未知功能的 C 端结构域，命名为 MUT7-C，附加在外切核糖核酸酶结构域上。我们的分析表明，MUT7-C 是古老的进化产物，因为在原核生物中存在一个作为单个蛋白的最小版本的结构域。在动物中，MUT7-C 获得了一个在进化过程中分化的插入，扩展了其功能。秀丽隐杆线虫的 MUT-7 在 MUT7-C 内包含一个特定的插入，允许与 MUT-8 结合，从而使 MUT-7 招募到生殖粒。此外，在秀丽隐杆线虫和人类 MUT-7 中，MUT7-C 结构域有助于 RNA 结合，因此对核糖核酸酶活性至关重要。这种 RNA 结合功能很可能代表了 MUT7-C 结构域的原始功能。总的来说，这项研究揭示了 MUT7-C，并为这个以前未被描述的结构域赋予了两个功能。
