Department of Life Science and Biotechnology, Jadavpur University, Kolkata, India.
Department of Life Science and Biotechnology, Jadavpur University, Kolkata, India.
J Mol Biol. 2018 Jul 6;430(14):1993-2013. doi: 10.1016/j.jmb.2018.05.009. Epub 2018 May 11.
Production of export-competent mRNAs involves transcription and a series of dynamic processing and modification events of pre-messenger RNAs in the nucleus. Mutations in the genes encoding the transcription and mRNP processing machinery and the complexities involved in the biogenesis events lead to the formation of aberrant messages. These faulty transcripts are promptly eliminated by the nuclear RNA exosome and its cofactors to safeguard the cells and organisms from genetic catastrophe. Mutations in the components of the core nuclear exosome and its cofactors lead to the tissue-specific dysfunction of exosomal activities, which are linked to diverse human diseases and disorders. In this article, we examine the structure and function of both the yeast and human RNA exosome complex and its cofactors, discuss the nature of the various altered amino acid residues implicated in these diseases with the speculative mechanisms of the mutation-induced disorders and project the frontier and prospective avenues of the future research in this field.
产生具有出口能力的 mRNAs 需要在细胞核中进行转录以及一系列前信使 RNA 的动态加工和修饰事件。编码转录和 mRNP 加工机制的基因突变以及生物发生事件的复杂性导致异常信息的形成。这些有缺陷的转录本会被核 RNA 外切体及其辅助因子迅速清除，以保护细胞和生物体免受遗传灾难。核心核外切体及其辅助因子的组成部分的突变导致外切体活性的组织特异性功能障碍，这与多种人类疾病和障碍有关。在本文中，我们研究了酵母和人类 RNA 外切体复合物及其辅助因子的结构和功能，讨论了这些疾病中涉及的各种改变的氨基酸残基的性质，以及推测突变引起的疾病的机制，并预测了该领域未来研究的前沿和前景方向。
