Intron‐Derived Lariat RNAs Go Stable

ABSTRACT During pre‐mRNA splicing, introns are removed by the spliceosome, and the flanking exons are ligated to form mature mRNA, which is subsequently translated into protein. Traditionally, intronic RNAs have been regarded as “junk”, presumed to be degraded for nucleotide turnover. Notably, after debranching, some linearized lariat RNAs can be further processed into snoRNAs, miRNAs, and other long non‐coding RNAs. However, recent studies have shown that many intron‐derived lariat RNAs can escape degradation and remain stable across various eukaryotic organisms, indicating they may play significant roles in cellular processes. Moreover, these naturally retained lariat RNAs are frequently observed in circular forms in vivo, suggesting that their linear tails are highly susceptible to degradation. This highlights lariat RNAs as an important source of circular RNAs. Furthermore, many lariat‐derived circRNAs have been detected in the cytoplasm, implying active nuclear export and potential roles in cytoplasmic processes. In this review, we provide an overview of the life cycle of intron‐derived lariat RNAs, focusing on their biogenesis, degradation, and retention. We also discuss the mechanisms that enable their resistance to degradation and the biological functions of stable lariat RNAs, shedding light on these seemingly “nonsense” yet inevitably produced non‐coding intronic RNAs.