Advances in Metabolism and Function of Lariat RNAs

Lariat RNAs are intrinsic products derived from excised introns during pre‑mRNA splicing. Fora long time, lariat RNAs were considered as non‑functional splicing by‑products. They are specifically recognizedby DBR1, the sole cellular debranching enzyme, which hydrolyzes their 2’‑5’ phosphodiester linkage, followedby rapid degradation by exonucleases. Complete loss‑of‑function of DBR1 results in global accumulation of lariatRNAs and embryonic lethality in both animals and plants. Cumulative evidence indicates that a subset of lariatRNAs in animals and plants can escape DBR1‑dependent debranching and degradation, stably accumulating incells and participating in diverse physiological and pathological processes. This review systematically summarizesthe structural features, substrate‑recognition specificity of DBR1 and regulatory modes mediated by its interactingproteins, and outlines state‑of‑the‑art techniques for genome‑wide identification of lariat RNAs. Multiple biologicalroles of lariat RNAs in posttranscriptional regulation are highlighted: serving as precursors for ncRNAs (non‑codingRNAs), cis‑activating host gene transcription, sustaining spliceosome recycling and splicing fidelity, and actingas molecular sponges or scaffolds to modulate the homeostasis of binding proteins and small RNAs. Based on the“kinetic competition model”, DBR1catalyzed debranching and nucleocytoplasmic trafficking of lariat RNAs arefurther discussed with respect to their comodulation of cellular homeostasis and pathological processes, includingneurodegenerative disorders, viral pathogenesis and stress responses. As a class of housekeeping‑like ncRNAs, de‑ciphering the metabolism and functional regulation of lariat RNAs helps deepen understanding of gene‑expressionplasticity, and provides new perspectives for comprehending general biological properties of lariat‑derived ncRNAsand exploring potential RNA‑based therapeutic targets.

CSTR: 10.11844/cjcb.2026.10.0001