The Widespread Impact of Mammalian MicroRNAs on mRNA Repression and Evolution

  title={The Widespread Impact of Mammalian MicroRNAs on mRNA Repression and Evolution},
  author={Kyle Kai-How Farh and Andrew Grimson and Calvin H. Jan and Benjamin P. Lewis and Wendy K. Johnston and Lee P. Lim and Christopher B. Burge and David P. Bartel},
  pages={1817 - 1821}
Thousands of mammalian messenger RNAs are under selective pressure to maintain 7-nucleotide sites matching microRNAs (miRNAs). We found that these conserved targets are often highly expressed at developmental stages before miRNA expression and that their levels tend to fall as the miRNA that targets them begins to accumulate. Nonconserved sites, which outnumber the conserved sites 10 to 1, also mediate repression. As a consequence, genes preferentially expressed at the same time and place as a… 

The evolving role of microRNAs in animal gene expression.

The authors conclude that many animal genes are under evolutionary pressure to maintain or avoid complementary sites to miRNAs, and the miRNA pathway broadly contributes to the complex gene regulatory networks that shape animal tissue development and identity.

Human microRNAs preferentially target genes with intermediate levels of expression and its formation by mammalian evolution

It is found that miRNAs preferentially target genes with intermediate levels of expression, while avoiding highly expressed ones, and that older miRNAAs have greater targeting specificity, suggesting that specificity increases during the course of evolution.

Interspecies regulation of microRNAs and their targets.

The Evolution of Imprinted microRNAs and Their RNA Targets

The 3′ UTR of PTEN, a gene with growth-related and metabolic functions, appears to be an important target of miRNAs from both clusters, and is illustrated using the examples of the imprinted C19MC cluster of mi RNAs in primates and C2MC cluster in mice that are paternally expressed in placentas.

The Importance of RNA Pairing Stability and Target Concentration for Regulation by MicroRNAs

Studies of lsy-6 targeting, conducted in human cell lines using heterologous reporter assays, are presented, which uncovered the reasons for this miRNA’s generally poor targeting proficiency and suggest a mechanism of repression of its in vivo targets that is more complex than for most other miRNAs.

Most mammalian mRNAs are conserved targets of microRNAs.

This work overhauled its tool for finding preferential conservation of sequence motifs and applied it to the analysis of human 3'UTRs, increasing by nearly threefold the detected number of preferentially conserved miRNA target sites.

The impact of microRNAs on protein output

The impact of micro RNAs on the proteome indicated that for most interactions microRNAs act as rheostats to make fine-scale adjustments to protein output.

The evolution and functional diversification of animal microRNA genes

Some of the many strategies that allow novel miRNA functions to emerge are described, with particular emphasis on how miRNA genes evolve in animals.

The relationship between the evolution of microRNA targets and the length of their UTRs

A systematic investigation of the relationship between miRNA regulation and their targets' evolution in two mammals: human and mouse finds genes with longer 3' UTRs are regulated by more distinct types of miRNAs.

An Evolutionary Perspective of Animal MicroRNAs and Their Targets

The genomic architecture of animal miRNA genes and their evolving interaction with their target mRNAs are discussed.



Specificity of microRNA target selection in translational repression.

The ability of an miRNA to translationally repress a target mRNA is largely dictated by the free energy of binding of the first eight nucleotides in the 5' region of the miRNA, however, G:U wobble base-pairing in this region interferes with activity beyond that predicted on the basis of thermodynamic stability.

Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes.

The results show that proximal pairs of miRNAs are generally coexpressed, and that in situ analyses of host gene expression can be used to probe the spatial and temporal localization of intronic mi RNAs.

Combinatorial microRNA target predictions

PicTar, a computational method for identifying common targets of micro RNAs, is presented and widespread coordinate control executed by microRNAs is suggested, thus providing evidence for coordinate microRNA control in mammals.

The functions of animal microRNAs

Evidence is mounting that animal miRNAs are more numerous, and their regulatory impact more pervasive, than was previously suspected.

MicroRNA Expression in Zebrafish Embryonic Development

Most miRNAs were expressed in a highly tissue-specific manner during segmentation and later stages, but not early in development, which suggests that their role is not in tissue fate establishment but in differentiation or maintenance of tissue identity.

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

These 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, and seem to downregulate a far greater number of targets than previously appreciated.

Principles of MicroRNA–Target Recognition

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.