Summary of canonical and splicing-mediated miRNA pathways. (A) Canonical miRNA hairpins are cleaved by Drosha to release a pre-miRNA hairpin, which is exported to the cytoplasm and cleaved by Dicer to release a miRNA/star duplex. One strand is preferentially loaded into an Argonaute (AGO) protein and guides it to targets. (B) Conventional mirtrons are short hairpin introns that are spliced and debranched to form a pre-miRNA hairpin, which then enters the canonical pathway. (C) With 5′- and 3′-tailed mirtrons, splicing generates only one end of the hairpin, with an unstructured “tail” that extends to the 3′ splice acceptor or 5′ splice donor, respectively. These require additional ribonucleolytic processing to generate the pre-miRNA hairpin.
