Question: Effect of the minimum free energy (MFE) on RNA stability
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gravatar for nadiabenjemii
8 months ago by
nadiabenjemii0 wrote:

Hi. What is the difference between free energy = -1478 kcal / mol and free energy = -1392 kcal / mol in terms of stability of a transcript and subsequently on protein expression? How can we relate this energy to highly structured and lowly structured transcripts?

rna-seq sequence gene • 280 views
ADD COMMENTlink modified 8 months ago • written 8 months ago by nadiabenjemii0
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gravatar for Mensur Dlakic
8 months ago by
Mensur Dlakic8.2k
USA
Mensur Dlakic8.2k wrote:

If my math is correct, the difference is 82 kcal/mol. That's probably not what you are asking. Both of these would be very stable structures. If I remember correctly, free energy of 16S rRNA is on the order of -200 kcal/mol, but you should verify that.

It is important to understand that stability of RNA molecules increases with their length, so it would not be surprising to me that a 20kB piece of mRNA could have this kind of stability. That does not mean necessarily that a ribosome couldn't translate that mRNA, because it has to surmount only parts of local structures as it goes rather than the whole thing at once.

ADD COMMENTlink written 8 months ago by Mensur Dlakic8.2k
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gravatar for nadiabenjemii
8 months ago by
nadiabenjemii0 wrote:

Thanks so much for your response. I would like to identify the effect of the synonymous mutation on the structure and thermodynamic characteristics of mRNA (using the RNAfold web server). I found that this mutation actually changes the mRNA sequence. But, could the decrease in MFE (-1478 Kcal / mol) suggest a decrease in mRNA stability and therefore a decrease in protein expression.

ADD COMMENTlink written 8 months ago by nadiabenjemii0

I can't imagine that a single mutation would cause that kind of MFE change. Nevertheless, the potential effect on translation will depend on many things, including the position of this mutation within the mRNA molecule. Generally speaking, mutations that increase mRNA stability closer to the ribosome binding site are more likely to significantly change expression. These papers may give you some idea about the effects of codon usage and mRNA folding stability on protein expression:

ADD REPLYlink written 8 months ago by Mensur Dlakic8.2k
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