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Dynamic isomiR regulation in Drosophila development

2010; Cold Spring Harbor Laboratory Press; Volume: 16; Issue: 10 Linguagem: Inglês

10.1261/rna.2379610

1469-9001

Selene L. Fernández-Valverde, Ryan J. Taft, John S. Mattick,

Cancer-related molecular mechanisms research

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.