Why do mutations not take place in mRNA of higher eukaryotes?

Question

Is it because it is too short-lived to be mutated? Both DNA and RNA are nucleic acids so how is mRNA protected? RNA viruses undergo mutations to evolve so I guess it is not immune to mutations

Answer 1

The premise of the questions suggests that mutations cannot take place in the mRNAs of higher eukaryotes. To answer your question I think it is important to consider two viewpoints:

First, from a theoretical point of view, since DNA and RNA are as you pointed out composed of nucleic acids, they both can be mutated if enough energy is provided (UV light, chemicals, etc) which invalidates the premise of the questions.

Now, from a practical point of view, as you mentioned most mRNAs molecules have a short half life typically in the minute to day range whereas DNA molecules exist during the whole existence of the organism.

While it can occurs that mRNAs are mutated people are not interested to study this aspect for the following reasons:

You pointed out in the comment section, a mutation in a mRNA molecule might lead to translated malformed protein which can easily be degraded. It will be only one mRNA transcript from thousands transcripts. With a short half life, the mRNA an proteins will be degraded which will not have a long standing impact of the cell/organism. As such it will be very difficult to observe a phenotype which will affect the whole host.

Thus RNAs mutations have only transient effects which will not affect the host in the long term. RNAs molecules are not more protected than DNA molecules just that they are short lived so the host is protected from the effects of RNA mutations.

Hope this helps!

Answer 2

Additionally DNA is inherently more stable due to the removal of the hydroxyl group from the C2 carbon on the ribose making it less reactive. This could be pointed to as an example of the limiting factor in the inherent complexity of any organism that uses RNA instead of DNA for long term data storage. That would be a discussion for another thread though.

Answer 3

Your supposition is incorrect. RNA does accumulate "mutations" because the RNA polymerase also makes errors. The misincorporation rate of bacterial RNA polymerase is ~10^–5 per nucleotide (Traverse & Ochman, 2016). Compared to that, DNA polymerase has much higher fidelity and has misincorporation of ~10^–10 per nucleotide per generation (Zhu et al., 2014).

As pointed out in the other answer, RNA mutational effects are short-lived as RNAs are short-lived. However, RNA mutations can contribute to phenotypic heterogeneity which can, in some cases, be beneficial to the organism (Ackermann, 2015).

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There is nothing special about higher eukaryotes as replication and transcription process is quite similar across different domains of life. Viruses are special, however. They rely on higher mutation rate for faster adaptation.

Answer 4

Mutations do occur in mRNA. This can occur during transcription, when RNA polymerase incorporates a non-cognate nucleotide into the nascent RNA strand (this may be because the DNA forms a short lived tautomer from quantum tunnelling, or because ). Alternatively, just like DNA bases, RNA bases are inherently unstable due to things like deamination events, but RNA is also capable of base catalyzed hydrolysis. To say that mutations are not interesting in RNA is also wrong as RNA editing is something that may be used to treat numerous diseases. RNA editing is transient, which is useful for treating diseases caused by temporary changes in cell state and modifying disease-related signal transduction through editing serine, threonine and tyrosine residues to affect phosphorylation sites. mRNA mutations are also important in understanding the affects of splicing on phenotypes and I'm sure there are more reasons, but these are just off the top of my head. For more information about RNA editing see: DOI: 10.1126/science.aaq0180, a really cool potential of CRISPR