mirtrons

Mirtrons are a class of microRNAs encoded within introns of protein-coding genes. Unlike canonical microRNAs, which are processed from primary transcripts by Drosha to generate a pre-miRNA hairpin, mirtrons enter the miRNA pathway via splicing and debranching.

After transcription, the host intron is removed by the spliceosome. The excised intron is debranched by the lariat-debranching enzyme DBR1 and then folds into a hairpin structure that resembles a canonical pre-miRNA. This hairpin is exported to the cytoplasm and diced by Dicer to produce a miRNA/miRNA* duplex, with the mature strand loaded into an Argonaute-containing effector complex.

Canonical mirtrons arise from short introns that can spontaneously form the hairpin after debranching. Tailed mirtrons contain cytoplasmic or nuclear tails that must be trimmed to generate a proper hairpin; these typically require additional exonucleolytic processing. Both canonical and tailed mirtrons bypass Drosha processing entirely.

Mirtrons have been identified in a variety of animals, including Drosophila and vertebrates, and constitute a subset of the miRNA repertoire. They illustrate an alternative route to miRNA maturation that links gene splicing to regulatory RNA production. The efficiency and expression of mirtrons can be influenced by intron turnover, splicing efficiency, and DBR1 activity; disruptions can affect miRNA levels and downstream gene regulation.

Because mirtrons rely on general RNA processing mechanisms, their presence expands the potential regulatory complexity of the transcriptome and reflects the evolutionary interconnection between splicing and RNA silencing pathways.