Abstract: 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.

Key words: 5′-to-3′, mRNA degradation, gene expression, eukaryotic mRNA, prokaryotic mRNA, drugs