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As I understand it, microRNAs are used to ensure that certain genes are only expressed when needed. The way this apparently works is that when the translation products of an mRNA are not required the appropriate microRNA is transcribed to bind to the mRNA and initiate its nucleolytic degradation.

My question is if the cell can detect that the product of a specific mRNA is not required why is the mRNA transcribed it all, rather than synthesizing it and then synthesizing another RNA to silence it?

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  • $\begingroup$ Hi Sam. I rolled back your recent edit, but I understand your frustration. Yours is an interesting question, though, as it stands, it is practically impossible to answer. If you reduce the scope of your question, you may find someone willing to take a crack at it. For instance, instead of asking why microRNAs exist (redundancy?), perhaps you can ask whether microRNA regulation is energetically beneficial from the cellular perspective, relative to control at the levels of transcription (TF abundance and binding) or translation. $\endgroup$
    – acvill
    Jun 13, 2022 at 18:10
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    $\begingroup$ @acvill: I disagree. It is not impossible to answer. miRNAs allow a cell to rapidly remove any present mRNA in order to react quickly. Furthermore, every mRNA is subject to constant production/degradation (RNA Homeostasis, Pelkmans 2022). This question is about RNA biochemistry. This does not contain an answer. $\endgroup$
    – markur
    Sep 5, 2022 at 7:14
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    $\begingroup$ @markur your comment addresses how miRNAs help maintain mRNA homeostasis. The question asks why miRNAs evolved as a control mechanism. We can speculate, but, generally, it’s very difficult to know why a particular trait or pathway evolved alongside / in lieu of another. $\endgroup$
    – acvill
    Sep 5, 2022 at 11:57
  • $\begingroup$ @markur if you believe the question should be reopened, feel free to submit an edit. $\endgroup$
    – acvill
    Sep 5, 2022 at 11:59
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    $\begingroup$ @acvill ok cool, I submitted an edit, let me know if I did something wrong. And sure, I get why one might consider this question is related to "traits". However, I feel it's unfair to depict this question as speculative, considered that there is just so much knowledge about how and why RNAs are produced and regulated and degraded etc. $\endgroup$
    – markur
    Sep 5, 2022 at 12:25

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Simple Answer

Switch On: To start expressing a protein-coding gene — synthesizing its product — you have at some stage to synthesize its mRNA — transcribe it.

Switch Off: To stop expressing a protein-coding gene it makes sense to stop making more RNA, as the poster suggests. But that may not be enough! Many eukaryotic mRNAs have half-lives ranging from hours to days, so that merely stopping transcription will not immediately stop the protein being produced. If it is important to stop synthesis immediately, something else is required. Nucleolytic degradation of the mRNA initiated by microRNAs is one way to do this.

More than one way to kill a cat

Why is this not more widespread? The answer is that this is only one of a variety of means to regulate gene expression. Others include having mRNAs of shorter half-life (as in bacteria), controlling mRNA translation, inactivation of the protein (if it is an enzyme) or degrading the product by proteolysis. Which method is employed depends on evolutionary chance, the nature of the system, whether it is advantageous to be able to resume activity quickly etc. So systems regulated by microRNA need to be considered on a case-by-case basis.

And although I am not competent to write on this (additions solicited) I am led to believe that mathematical modelling shows that the existence of a variety of regulatory mechanisms can allow a smoother and more buffered response to a variety of stimuli.

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The key differences are:

  • miRNA act very quickly (hours, day). Transcriptional repression stops production, but doesn‘t remove the gene‘s signal since the mRNA is still there.
  • one miRNA can target multiple (even hundreds of) different transcripts coming from different genomic loci, causing significant changes to the transcriptome at once. That‘s needed for differentiation processes (see let-7: Balzeau 2017). Transcriptional repression can‘t handle that, since that would impose more extensive requirements on promoters/enhancers. (Ni & Leng 2015)
  • miRNA evolved from an anti-viral system (RNA interference) that degrades viral dsRNA. Its machinery is multifunctional.
  • miRNA can be transported between cells within extracellular vesicles. That way, intercellular communication causes quick changes to transcriptomes. Transcriptional repressors can‘t do that as easily, since they‘re localized to the nucleus and not the cytosol.
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