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Widespread regulatory activity of vertebrate microRNA* species. RNA

Department of Developmental Biology, Sloan-Kettering Institute, New York, New York 10065, USA.
RNA (Impact Factor: 4.62). 02/2011; 17(2):312-26. DOI: 10.1261/rna.2537911
Source: PubMed

ABSTRACT An obligate intermediate during microRNA (miRNA) biogenesis is an ~22-nucleotide RNA duplex, from which the mature miRNA is preferentially incorporated into a silencing complex. Its partner miRNA* species is generally regarded as a passenger RNA, whose regulatory capacity has not been systematically examined in vertebrates. Our bioinformatic analyses demonstrate that a substantial fraction of miRNA* species are stringently conserved over vertebrate evolution, collectively exhibit greatest conservation in their seed regions, and define complementary motifs whose conservation across vertebrate 3'-UTR evolution is statistically significant. Functional tests of 22 miRNA expression constructs revealed that a majority could repress both miRNA and miRNA* perfect match reporters, and the ratio of miRNA:miRNA* sensor repression was correlated with the endogenous ratio of miRNA:miRNA* reads. Analysis of microarray data provided transcriptome-wide evidence for the regulation of seed-matched targets for both mature and star strand species of several miRNAs relevant to oncogenesis, including mir-17, mir-34a, and mir-19. Finally, 3'-UTR sensor assays and mutagenesis tests confirmed direct repression of five miR-19* targets via star seed sites. Overall, our data demonstrate that miRNA* species have demonstrable impact on vertebrate regulatory networks and should be taken into account in studies of miRNA functions and their contribution to disease states.

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Available from: Michael D Phillips, Jul 15, 2014
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    • "miRNA* was assumed to be a passenger strand rapidly degraded after binding of the miR- NA to argonaut protein (Jones-Rhoades et al., 2006). However, a number of recent papers have shown that some miRNA*s are functional in gene regulation (Devers et al., 2011; Yang et al., 2011). To differentiate functional miRNA*, the designation was proposed where -5p and/or -3p is added to distinguish those miRNA products from each arm. "
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    New Phytologist 03/2015; DOI:10.1111/nph.13365 · 7.67 Impact Factor
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    • "miRNA* was assumed to be a passenger strand rapidly degraded after binding of the miR- NA to argonaut protein (Jones-Rhoades et al., 2006). However, a number of recent papers have shown that some miRNA*s are functional in gene regulation (Devers et al., 2011; Yang et al., 2011). To differentiate functional miRNA*, the designation was proposed where -5p and/or -3p is added to distinguish those miRNA products from each arm. "
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    ABSTRACT: Plant microRNAs (miRNAs) play important regulatory roles in a number of developmental processes. The present work investigated the roles of miRNAs during nodule development in the crop legume soybean (Glycine max). Fifteen soybean small RNA libraries were sequenced from different stages of nodule development, including young nodules, mature nodules and senescent nodules. In order to identify the regulatory targets of the miRNAs, five parallel analysis of RNA ends (PARE) libraries were also sequenced from the same stages of nodule development. Sequencing identified 284 miRNAs, including 178 novel soybean miRNAs. Analysis of miRNA abundance identified 139 miRNAs whose expression was significantly regulated during nodule development, including 12 miRNAs whose expression changed > 10-fold. Analysis of the PARE libraries identified 533 miRNA targets, including three nodulation-related genes and eight nodule-specific genes. miR393j-3p was selected for detailed analysis as its expression was significantly regulated during nodule formation, and it targeted a nodulin gene, Early Nodulin 93 (ENOD93). Strong, ectopic expression of miR393j-3p, as well as RNAi silencing of ENOD93 expression, significantly reduced nodule formation. The data indicate that miR393j-3p regulation of ENOD93 mRNA abundance is a key control point for soybean nodule formation.
    New Phytologist 02/2015; · 7.67 Impact Factor
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    • "However, several studies have suggested that miRNA∗ strands are more abundant than initially thought and that these might be more than mere carriers of the guide strand. Comparisons between human, chimpanzee, mouse, rat, dog, and chicken genomes revealed that several human miRNA∗ strands are highly conserved, especially at the seed sequence vicinity, which, in turn, exhibits significant 3′UTR complementarity across vertebrate evolution (Yang et al., 2011). miRNA∗ seed sequences and center regions have also been shown to be conserved across Drosophilid evolution (Okamura et al., 2008) and a group of typical vertebrates (human, zebrafish, chicken, and frog; Guo and Lu, 2010). "
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