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What this does, as a non-biotech person, I believe I understand at a high level: plonk this code into a ribosome and out comes the desired protein.

What I don't understand is:

   a) how the m-RNA code relates to the produced protein (i.e I can read C-code and get an idea of what is does fairly quickly, but can the same be said of m-RNA and the resulting protein)?

   b) how did they get their hands on that code in the first place? Do the coronaviruses use m-RNA as well? Was then a coronavirus somehow "dissected" to get at the spike protein "source code"?


Answers:

a) From the mRNA you can learn the amino acid sequence of the protein very quickly. You absolutely cannot (yet) learn the function of the protein from that sequence - normally, people just do comparisons with proteins whose functions ARE known. Oftentimes in enzymes there are "domains" or little functional regions that stay consistent over long periods of time, so that's a good way to assign function (given knowledge of other proteins in the same family)

b) Yep. Every virus at some point in their lifecycle use mRNA. You can just sequence the virus and get all that data (I've done that on SARS-COV-2, it's honestly pretty easy). Then you just do homology alignment (as stated above) and you can figure out approximately what each gene does.

The problem of de-novo protein prediction is ONE OF THE HARDEST PROBLEMS IN BIOTECH, but just like getting amino acid sequence, doing homology searches, sequencing viruses, etc, is basic biotech and I'd expect an eager high schooler or undergrad to be able to do them.


Thanks !


a) I don't know if protein-folding software is good enough to figure out the exact structure of the resulting protein given just the gene, but I suspect you could figure out through the equivalent of the strings command - looking for sub-chains of the protein, and looking for matching sequences in the gene

b) Coronaviruses happen to be RNA viruses; that is, their genomes are RNA rather than DNA. DNA viruses also exist and are common. We got full genomes from sequencing early in the pandemic, and continue to use it to monitor the evolution of the virus (see e.g. [1], where the results are available for download). Sequencing is very cheap and easy these days - you take a sample from a patient, use chemicals to break down all the cell membranes and such, sequence all of the DNA and RNA in it, and look through the results for a virus genome (i.e. something that isn't a human chromosome and isn't a known virus or bacterial genome). "m"RNA is more a description of the function than the chemical - tRNA and rRNA are short snippets of RNA used for manufacturing purposes inside the cell, while mRNA is the long chunks that actually carry information from the DNA to the protein manufacturing sites. Virus RNA basically functions as imposter mRNA, getting those manufacturing systems to make more viruses.

[1] https://www.ncbi.nlm.nih.gov/datasets/coronavirus/genomes/ - SARS-CoV-2 is the COVID-19 virus. As of my fetch, there are 71,509 full sequences of the virus, reflecting slight mutations over time and space.


a) Yes, you can translate a mature[1] mRNA sequence, codon by codon, from the start until the stop codon, and it will give you the sequence of the protein it encodes.

b) Coronaviruses have a RNA genome. Researchers extracted it from wild-type viruses and then sequenced it.

[1]: mRNAs can undergo several maturation steps, such as splicing, which removes regions that won’t be translated into protein.


Everyone else has had good answers, but I'm also going to note that we knew a ton about covid's general molecular biology well before it ever came into existence. Covid (more properly, SARS-CoV-2) is a cronovirus. Cronoviruses have been studied for some time since some of them cause common colds, and studied very intensely since 2002 when SARS showed pandemic potential. So when Covid showed up, there was a ton of prestablished information and expertise avaliable to help every element of the pandemic response.




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