RNA降解是基因表达调节的重要途径,影响很多生命活动。近来,mRNA降解机制有了很多新发现,如真核生物中发现了一种mRNA末端尿苷化介导的脱帽机制,和一条不依赖exosome的3′→5′的mRNA降解途径。虽然真核生物与原核生物mRNA降解途径非常相似,通常都有3种：内切降解、5′→3′外切降解和3′→5′外切降解等,但两者mRNA降解途径之间也存在很多差异,如5′→3′方向的外切降解是真核生物mRNA最重要的降解途径之一,但其在细菌中作用非常弱,且只在革兰氏阳性菌中发现。mRNA降解的研究不仅深化了人们对这一过程的认识,而且有助于新型药物的研发,以防御寄生虫、病毒或治疗人类疾病(如癌症)等。文章主要综述了真核生物和原核生物mRNA 5′→3′方向的降解机制,并对其应用前景进行了展望。
RNA degradation plays an important role in modulating gene expression and it affects multiple biological processes. There are three common degradation mechanisms of eukaryotic and prokaryotic mRNA: endonucleolytic, 5′-to-3′ and 3′-to-5′ exonucleolytic degradation. Differences do exist between the two kingdoms. For example, although the 5′-to-3′ exoribonucleolytic degradation is the primary degradation mechanism of eukaryotic mRNA, it plays a minimal role in bacteria, and only in Gram-positive bacteria. Recently, novel RNA degradation mechanisms have been revealed, such as a new eukaryotic mRNA decapping mode mediated by 3′-uridylation and a new 3′-to-5′ degradation pathway independent of exosome. These accumulating discoveries not only deepen the insight of mRNA degradation mechanisms, but also may contribute to the development of novel therapeutic drugs targeting parasites, viruses or cancer. In this review, we summarize the current knowledge of 5′-to-3′ exonucleolytic degradation pathway of eukaryotic and prokaryotic mRNA, and its future therapeutic perspectives.
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