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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.

SUBMITTER: Fernandez-Valverde SL

PROVIDER: S-EPMC2941097 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Dynamic isomiR regulation in Drosophila development.

Fernandez-Valverde Selene L SL Taft Ryan J RJ Mattick John S JS

RNA (New York, N.Y.) 20100830 10

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 developmen ...[more]

PMID: 20805289

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Project description:BackgroundGene expression patterns are determined by rates of mRNA transcription and decay. While transcription is known to regulate many developmental processes, the role of mRNA decay is less extensively defined. A critical step toward defining the role of mRNA decay in neural development is to measure genome-wide mRNA decay rates in neural tissue. Such information should reveal the degree to which mRNA decay contributes to differential gene expression and provide a foundation for identifying regulatory mechanisms that affect neural mRNA decay.ResultsWe developed a technique that allows genome-wide mRNA decay measurements in intact Drosophila embryos, across all tissues and specifically in the nervous system. Our approach revealed neural-specific decay kinetics, including stabilization of transcripts encoding regulators of axonogenesis and destabilization of transcripts encoding ribosomal proteins and histones. We also identified correlations between mRNA stability and physiologic properties of mRNAs; mRNAs that are predicted to be translated within axon growth cones or dendrites have long half-lives while mRNAs encoding transcription factors that regulate neurogenesis have short half-lives. A search for candidate cis-regulatory elements identified enrichment of the Pumilio recognition element (PRE) in mRNAs encoding regulators of neurogenesis. We found that decreased expression of the RNA-binding protein Pumilio stabilized predicted neural mRNA targets and that a PRE is necessary to trigger reporter-transcript decay in the nervous system.ConclusionsWe found that differential mRNA decay contributes to the relative abundance of transcripts involved in cell-fate decisions, axonogenesis, and other critical events during Drosophila neural development. Neural-specific decay kinetics and the functional specificity of mRNA decay suggest the existence of a dynamic neurodevelopmental mRNA decay network. We found that Pumilio is one component of this network, revealing a novel function for this RNA-binding protein.

Dataset Information

Dynamic isomiR regulation in Drosophila development.

Publications

Dynamic isomiR regulation in Drosophila development.

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