无义mRNA降解途径的机制与进化

摘要

The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs),but also regulates the abundance of a large number of cellular physiological mRNAs.The core of NMD pathway is the recognition and degradation of nonsense mRNA,and the function and regulation mechanism of the key factors UPFs and SMGs becomes the focus of NMD research area.The mechanism of NMD is conserved in organisms,while have differences in organisms at different evolutionary status,indicating evolutionary characteristics of the NMD pathway.The most research progresses of NMD mechanism were made from high eukaryotes,but little is known in protozoan.The researches on the function and evolution of core components of NMD using model organisms will help us unveil the function and regulatory mechanism of NMD,and establish the NMD network in humans to provide the theoretical basis for prevention and treatment of genetic diseases and cancers.%含有无义突变的mRNA在细胞中被无义介导的mRNA降解(nonsense-mediated mRNA decay,NMD)途径选择性降解,同时该途径还能调控细胞中一些生理性RNA的丰度.NMD途径的核心是含有无义突变的mRNA的识别和降解机制,其中关键因子上游移码蛋白(up-frameshift,UPF)和生殖器形态效应抑制因子(suppressor with morphological effect on genitalia,SMG)的功能及其调控机制是NMD途径研究的热点问题.NMD途径核心因子的种类和功能在不同进化地位的生物中既有一定的保守性,也有一定的差异,说明NMD途径具有一定的进化学特征.高等真核生物NMD途径机制的研究取得了一定的进展,而在原生生物中尚无机制层面的研究.利用原生动物作为模式生物开展NMD途径关键因子的功能和进化研究,有助于从进化学角度揭示NMD途径的功能和调控机制,为建立人类细胞中NMD途径的调控网络提供数据支持,为人类遗传学疾病和肿瘤的预防和治疗提供理论基础.