Principles of MicroRNA–Target Recognition
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The minimal requirements for functional miRNA–target duplexes in vivo are evaluated and classes of target sites with different functional properties are distinguished, indicating that miRNAs regulate a large fraction of protein-coding genes and that miRNA 3′ ends are key determinants of target specificity within miRNA families.Abstract:
MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression in plants and animals. Although their biological importance has become clear, how they recognize and regulate target genes remains less well understood. Here, we systematically evaluate the minimal requirements for functional miRNA–target duplexes in vivo and distinguish classes of target sites with different functional properties. Target sites can be grouped into two broad categories. 5′ dominant sites have sufficient complementarity to the miRNA 5′ end to function with little or no support from pairing to the miRNA 3′ end. Indeed, sites with 3′ pairing below the random noise level are functional given a strong 5′ end. In contrast, 3′ compensatory sites have insufficient 5′ pairing and require strong 3′ pairing for function. We present examples and genome-wide statistical support to show that both classes of sites are used in biologically relevant genes. We provide evidence that an average miRNA has approximately 100 target sites, indicating that miRNAs regulate a large fraction of protein-coding genes and that miRNA 3′ ends are key determinants of target specificity within miRNA families.read more
Citations
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MicroRNAs: Target Recognition and Regulatory Functions
TL;DR: The current understanding of miRNA target recognition in animals is outlined and the widespread impact of miRNAs on both the expression and evolution of protein-coding genes is discussed.
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TL;DR: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators as discussed by the authors, and have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.
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Oncomirs — microRNAs with a role in cancer
TL;DR: Evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes.
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Predicting effective microRNA target sites in mammalian mRNAs
TL;DR: It is shown that recently reported non-canonical sites do not mediate repression despite binding the miRNA, which indicates that the vast majority of functional sites are canonical.
References
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TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
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The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14
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TL;DR: Evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.
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TL;DR: The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.
Journal ArticleDOI
The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans
Brenda J. Reinhart,Frank J. Slack,Frank J. Slack,Michael Basson,Amy E. Pasquinelli,Bettinger Jc,Ann E. Rougvie,H R Horvitz,Gary Ruvkun +8 more
TL;DR: It is shown that let-7 is a heterochronic switch gene that encodes a temporally regulated 21-nucleotide RNA that is complementary to elements in the 3′ untranslated regions of the heteroch chronic genes lin-14, lin-28, Lin-41, lin -42 and daf-12, indicating that expression of these genes may be directly controlled by let- 7.