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During the last two months I have read several papers on miRNAs. I noticed miRNAs because they compose an important part of gene regulatory networks and recent discoveries have shown miRNA manipulation can do the job of the transcription factor (TF) routine (developed by Yamanaka's group since 2006) in cell reprogramming (Anokye-Danso et al., 2011). It will be beneficial to understand how miRNAs could do the similar things as what TFs can do in terms of gene expression regulation, as well as how different they are in their ways of functioning.

Professor Oliver Hobert wrote a review in 2008 elaborating the similarities and differences between miRNAs and TFs in their ways of gene expression regulation. From his review I learned that miRNAs and TFs both compose similar motifs of regulatory networks in terms of topology and that they might have the same target genes. Besides this, miRNAs may cross link with TFs widely, composing more complex motifs and functioning coordinatingly with TFs, rather than play as a separate layer of the regulatory networks.

As learned from Hobert's review, the differences between miRNAs and TFs lie in several aspects.

1) The target loci. -- The sizes of TF targets are often 'dozens of kilobases' while those of miRNA targets are less than 1Kbp. Besides, TFs usually bind with the 5' upstream region of the target gene while miRNAs usually bind with the 3' UTFs of the target messenger RNAs.

2) Efficiency, precision and speed. -- TFs have to be translated in cytoplasm (escaping any possible miRNA repression) and then transported back into nucleus to perform their functions, while miRNAs can function just within the cytoplasm, or even more precisely in particular compartment of the cell. As the result, TF regulation may experience more noise and a higher possibility of interruption, while miRNAs may function with less noise and more instantly upon any signals from outside.

3) Reversibility. -- miRNA-mediated repression may be relieved more rapidly (if possible) than TF-mediated repression.

4) In terms of evolution -- miRNAs have smaller sizes and a non-conding nature thus may be more likely to emerge by mutation than TFs which have longer target-recognizing sequences.

5) In terms of related phenotype defects -- miRNAs are less likely to cause essential developmental failures than TFs (see cited original reports from Miska et al. 2007 and www.wormbase.org). I keep my doubt to this claim because 80% * 90% seems not so different from 70%, although I wish I could accept it.

In addition, some of the above points are side-supported by another review by Peterson et al. in 2007. In the fantastic paper, the evolutionist authors correlated miRNAs with the evolutionary history of multi-cellular organisms and found that the emergence of miRNAs generally reduce expression noise of the related genes. And indeed, bigger miRNA families emerged more rapidly in more recent taxa, which is related to higher complexity due to more preciesly controled differentiation of new sets of terminal cell types.

So generally, could we say that miRNAs are more recently evolved, more related to terminal cell types, more related to precisely, rapid and reversible gene expression regulation than TFs? And, as evolution is going on, is it possible that miRNAs could play the roles of TFs and finally replace the latter?

At first glance it is contradictory to the claim in the above 4) that most miRNAs don't play vital roles in development. And it seems miRNAs are only the leaves and fine twigs while TFs construct the major branches of the 'tree' of regulatory networks. But considerring the recent advances of miRNA-mediated reprogramming, things are not so impossible and small twigs can also grow to be big branches.

Personally I think, even if it is untrue and impossible, at least it gives some hint to future bio-technology, by which we could devise an organism without TFs but only miRNAs composing its genome regulatory networks.

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