Analysis of Nearly One Thousand Mammalian Mirtrons Reveals Novel Features of Dicer Substrates
Fig 1
Examples of novel mirtrons confidently annotated in this study.
(A) Drosha-mediated and splicing-mediated pathways for the generation of Dicer-substrate pre-miRNA hairpins. For both canonical miRNA loci and mirtron loci of all four classes, the critical judgement for their annotation is whether the small RNA evidence supports the notion that their progenitor hairpins were subject to Dicer cleavage to generate specific miRNA/miRNA* (star) duplexes. The thickness of the arrows leading to Dicer indicates the relative number of substrates generated by each pathway. (B) Mirtron supported by especially robust evidence, including the presence of both miRNA and star reads in Ago-IP data and the recovery of abundant phased loop reads. Note that loop reads were not found in the Ago-IP data, providing evidence for the selection of specific species in Ago complexes. (C) A mirtron locus lacking substantial "star" read evidence, whose confidence is bolstered by hundreds of reads in Ago-IP libraries. (D) Example of a skin-restricted mirtron whose reads are highly represented in Ago1-IP, Ago2-IP and Ago3-IP data. (E) Example of a heart-restricted mirtron. Over 96% of reads collected from nearly 700 human small RNA datasets were from heart. (F) Example of a "two-tailed" mirtron supported by abundant Ago-IP reads. We infer that generation of the pre-miRNA involves splicing followed by removal of both 5' and 3' tails (see A).