miRNAs control various physiological and pathological processes, but what controls microRNAs? What controls their switch-on switch off? Is there any miRNA which can be termed as a "super" miRNA that regulates the expression of all other miRNAs?
Hi Ashraf
Great question !!!!... It appear not to exist any super miRNA that regulates the expression of others. miRNAs are genes and normally their expression is controlled by transcription factors. However there are several accessory factors that can control the expression of miRNAs..
Look at this paper by the group of Javier Caceres. They describe a protein that binds to the hairpin loop of mir18 stimulating its processing. So this is an elegant mechanism of controlling expression of a miR.
http://www.ncbi.nlm.nih.gov/pubmed/21755470
You have to think in miRNAs always in a very integrative manner. Their regulatory control over mRNAs is also very gentle and soft, it is not a switch. One single miRNA acting over a single target could reduce the protein output in 15-20%.
So... just to finish, if you think about a SUper miRNAs its regulatory effect over others will need always to be indirect (mediated by proteins or other ncRNAs). So... I think that is not very probable to exist.
Cheers. Paco
Hi Francisco,
Thanks for your answer and the link. I am trying to understand deeply about miRNAs. More I read about them, more I get fascinated how such a small molecule can even change cellular phenotype and so on.. I am still infant in this field and want to acquire the maximum knowledge.
Thanks.
Ash
For sure is fascinating. You should think "big".... miRNAs are controlling not only individual genes but more pathways and networks. So this is a concept for systems biology, and that is the main reason because they are so difficult to understand. Looks that all miRNAs together in a particular cell work to maintain homeostasis in the genomic output.
Dear Dr. Francisco,
I have seen one paper, in which one micro RNA regulating other's biogenesis, kindly have look-
http://www.nature.com/cr/journal/v22/n3/full/cr2011137a.html
Hi Sushil
Many, many thanks for the post... Very interesting... Looks that I have to retract my affirmations ... :)
Looks that we are dealing with a particular case, however it could be furthermore extended to other miRNAs. I am not sure if the authors showed enough evidence of the involvement of other lncRNAs in this control.... It is known that AGO family of proteins can bind small ncRNAs in the nucleus and exert epigenetic control over chromatin regions (RITS complex). Could be an AGO mediated mechanism ??
Interestingly in the paper, the authors claim that the binding of the miRNA to the target is exerted over the pri-miRNA... opening the possibility of existance of regulatory sequences within it ....
Many thanks again ... That's science !!!. Open for discussions !!!
Cheers.
For more information on biogenesis (http://www.nature.com/nrg/journal/v11/n9/full/nrg2843.html)
This is getting more and more interesting!
Very nice overview by Maria giving an indication and supporting justification for let-7 as a putative master-miRNA. You never know, may be one day we come across such condition where we just try to control or maintain the expression of one such miRNA and it will take care of other downstream regulatory pathways to prevent or protect against pathological conditions.
Pri-miRNA structure can also play a role in regulating miRNAs.
See: Role of pri-miRNA tertiary structure in miR-17~92 miRNA biogenesishttp://www.ncbi.nlm.nih.gov/pubmed/21955497
What place does the regulation of gene activity by small RNAs compared to the classical method of regulation by activators, repressors, transcription factors? Small RNAs work together or instead of the classic controller or in special places?
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