title: Dynamic isomiR regulation in Drosophila development.
abstract: Several recent reports have demonstrated that microRNAs (miRNAs) can exhibit heterogeneous ends and post-transcriptional nontemplate 3' end additions of uridines or adenosines. Using two small RNA deep-sequencing data sets, we show here that these miRNA isoforms (isomiRs) are differentially expressed across Drosophila melanogaster development and tissues. Specifically, we demonstrate that: (1) nontemplate nucleotide additions of adenosines to miRNA 3' ends are highly abundant in early development; (2) a subset of miRNAs with nontemplate 3' Us are expressed in adult tissues; and (3) the size of at least eight "mature" (unmodified) miRNAs varies in a life-cycle or tissue-specific manner. These results suggest that subtle variability in isomiR expression, which is widely thought to be the result of inexact Dicer processing, is regulated and biologically meaningful. Indeed, a subset of the miRNAs enriched for 3' adenosine additions during early embryonic development, including miR-282 and miR-312, show enrichment for target sites in developmental genes that are expressed during late embryogenesis, suggesting that nontemplate additions increase miRNA stability or strengthen miRNA:target interactions. This work suggests that isomiR expression is an important aspect of miRNA biology, which warrants further investigation.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia.
authors.forename: Selene L
authors.initials: SL
authors.lastname: Fernandez-Valverde
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Taft
authors.forename: John S
authors.initials: JS
authors.lastname: Mattick
mesh_terms: D000818:Animals; D001483:Base Sequence; D019295:Computational Biology; D030561:Databases, Nucleic Acid; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D008297:Male; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012689:Sequence Homology, Nucleic Acid
chemical_list: D035683:MicroRNAs
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