DBR1 orchestrates the fate of lariat RNA: debranching-dependent turnover and function

Lariat RNA, formed from excised introns during RNA splicing, is produced in molar amounts equal to mature messenger RNAs. As most genes contain introns in higher eukaryotes, lariat RNAs are inevitably generated and exhibit sequence diversity during gene expression. In general, lariat RNA is specifically debranched by the RNA debranching enzyme DBR1, followed by exonuclease-mediated degradation. DBR1 is the sole enzyme responsible for lariat RNA turnover. The recognition and debranching of lariat RNA by DBR1 is completely dependent on the existence of the branch structure with a 2'-5' phosphodiester bond. Surprisingly, recent advances have shown that some lariat RNAs can escape debranching and accumulate in a circular form from plants to mammals. We revisit the identification and functional regulation of DBR1, summarize the methods for defining and detecting lariat RNA, and highlight the extrinsic mechanisms and biological significance of DBR1-mediated lariat RNA debranching and lariat RNA retention. As an archetype of housekeeping noncoding RNAs, understanding lariat RNA turnover provides insights into the general properties of other noncoding RNA, especial circular RNA.