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Abstract

As the number of known microRNAs (miRNAs) increases, and their importance in physiology and disease becomes apparent, the identification of their regulatory targets is a requisite for a full characterization of their biological functions. Computational methods based on sequence homology and phylogenetic conservation have spearheaded this effort in the last 3 years, but they may not be sufficient. Experimental studies are now needed to extend and validate the computational predictions and further our understanding of target recognition by miRNAs.

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Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.

Lee P. Lim, Nelson C. Lau, Philip Garrett-Engele … (2005)

MicroRNAs (miRNAs) are a class of noncoding RNAs that post-transcriptionally regulate gene expression in plants and animals. To investigate the influence of miRNAs on transcript levels, we transfected miRNAs into human cells and used microarrays to examine changes in the messenger RNA profile. Here we show that delivering miR-124 causes the expression profile to shift towards that of brain, the organ in which miR-124 is preferentially expressed, whereas delivering miR-1 shifts the profile towards that of muscle, where miR-1 is preferentially expressed. In each case, about 100 messages were downregulated after 12 h. The 3' untranslated regions of these messages had a significant propensity to pair to the 5' region of the miRNA, as expected if many of these messages are the direct targets of the miRNAs. Our results suggest that metazoan miRNAs can reduce the levels of many of their target transcripts, not just the amount of protein deriving from these transcripts. Moreover, miR-1 and miR-124, and presumably other tissue-specific miRNAs, seem to downregulate a far greater number of targets than previously appreciated, thereby helping to define tissue-specific gene expression in humans.

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Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.

Bruce Wightman, Ilho Ha, Gary Ruvkun (1993)

During C. elegans development, the temporal pattern of many cell lineages is specified by graded activity of the heterochronic gene Lin-14. Here we demonstrate that a temporal gradient in Lin-14 protein is generated posttranscriptionally by multiple elements in the lin-14 3'UTR that are regulated by the heterochronic gene Lin-4. The lin-14 3'UTR is both necessary and sufficient to confer lin-4-mediated posttranscriptional temporal regulation. The function of the lin-14 3'UTR is conserved between C. elegans and C. briggsae. Among the conserved sequences are seven elements that are each complementary to the lin-4 RNAs. A reporter gene bearing three of these elements shows partial temporal gradient activity. These data suggest a molecular mechanism for Lin-14p temporal gradient formation: the lin-4 RNAs base pair to sites in the lin-14 3'UTR to form multiple RNA duplexes that down-regulate lin-14 translation.

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An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.

N. Lau, L. P. Lim, E G Weinstein … (2001)

Two small temporal RNAs (stRNAs), lin-4 and let-7, control developmental timing in Caenorhabditis elegans. We find that these two regulatory RNAs are members of a large class of 21- to 24-nucleotide noncoding RNAs, called microRNAs (miRNAs). We report on 55 previously unknown miRNAs in C. elegans. The miRNAs have diverse expression patterns during development: a let-7 paralog is temporally coexpressed with let-7; miRNAs encoded in a single genomic cluster are coexpressed during embryogenesis; and still other miRNAs are expressed constitutively throughout development. Potential orthologs of several of these miRNA genes were identified in Drosophila and human genomes. The abundance of these tiny RNAs, their expression patterns, and their evolutionary conservation imply that, as a class, miRNAs have broad regulatory functions in animals.

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PubMed ID:: 17381288

DOI:: 10.1101/sqb.2006.71.032

ScienceOpen disciplines: Chemistry

Keywords: Animals,Caenorhabditis elegans,genetics,Caenorhabditis elegans Proteins,Computational Biology,Gene Expression Regulation,Genes, Helminth,Humans,MicroRNAs,metabolism,Nuclear Proteins,RNA-Induced Silencing Complex

MicroRNAs in search of a target.

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Abstract

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Most cited references 49

Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.

Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.

An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.

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