Analysis of Nearly One Thousand Mammalian Mirtrons Reveals Novel Features of Dicer Substrates

PLoS Computational Biology
Jiayu WenEric C Lai

Abstract

Mirtrons are microRNA (miRNA) substrates that utilize the splicing machinery to bypass the necessity of Drosha cleavage for their biogenesis. Expanding our recent efforts for mammalian mirtron annotation, we use meta-analysis of aggregate datasets to identify ~500 novel mouse and human introns that confidently generate diced small RNA duplexes. These comprise nearly 1000 total loci distributed in four splicing-mediated biogenesis subclasses, with 5'-tailed mirtrons as, by far, the dominant subtype. Thus, mirtrons surprisingly comprise a substantial fraction of endogenous Dicer substrates in mammalian genomes. Although mirtron-derived small RNAs exhibit overall expression correlation with their host mRNAs, we observe a subset with substantial differences that suggest regulated processing or accumulation. We identify characteristic sequence, length, and structural features of mirtron loci that distinguish them from bulk introns, and find that mirtrons preferentially emerge from genes with larger numbers of introns. While mirtrons generate miRNA-class regulatory RNAs, we also find that mirtrons exhibit many features that distinguish them from canonical miRNAs. We observe that conventional mirtron hairpins are substantially longer ...Continue Reading

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Datasets Mentioned

BETA
ERP000546
GSE45506

Methods Mentioned

BETA
RNA-seq
sRNA-seq

Software Mentioned

IP
Bowtie
Ago
UCSC Genome Browser
R package
Mirtron
TopHat

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