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Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

bioinformatics.stackexchange.com

51–60 of 125 posts

Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#51

The top answer at the link explains it best: Good observation! The 3' poly(A) tail is actually a very common feature of positive-strand RNA viruses, including coronaviruses and picornaviruses. For coronaviruses in particular, we know that the poly(A) tail is required for replication, functioning in conjunction with the 3' untranslated region (UTR) as a cis-acting signal for negative strand synthesis and attachment to…

Can a drug target that sequence specifically?

Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#52
post #51

The top answer at the link explains it best: Good observation! The 3' poly(A) tail is actually a very common feature of positive-strand RNA viruses, including coronaviruses and picornaviruses. For coronaviruses in particular, we know that the poly(A) tail is required for replication, functioning in conjunction with the 3' untranslated region (UTR) as a cis-acting signal for negative strand synthesis and attachment to…

Can a drug target that sequence specifically?

No

Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#53
post #51

Earlier quoted context omitted.

Can a drug target that sequence specifically?

No

Is it that simple? From a lay perspective (and granted I’m a little foggy because I actually have covid right now), I’d expect the answer is yes but with huge unintended consequences.

Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#54

Earlier quoted context omitted.

The stop codon is more like the '\n' or '\0' in computing. Polya tails protect against degradation and is used for nuclear export of RNA.

This is true, but perhaps worth noting the nuclear transport function of polyA tails don't come into play for coronavirus. The payload of coronavirus is a positive-sense single-stranded RNA. Which means it does not need to enter the nucleus for preprocessing and can basically just start replicating shortly after entering a cell. See diagram... https://upload.wikimedia.org/wikipedia/commons/f/f4/Coronavi... There migh…

I don't think the genome has a specific length of the tail (33 is a consensus length)

During genomic assays, the poly a tail will not be a specific length, but a single consensus sequence is still provided.

This was also posted in the first comment:

> Similar to eukaryotic mRNA, the positive-strand coronavirus genome of ~30 kilobases is 5’-capped and 3’-polyadenylated. It has been demonstrated that the length of the coronaviral poly(A) tail is not static but regulated during infection; however, little is known regarding the factors involved in coronaviral polyadenylation and its regulation. Here, we show that during infection, the level of coronavirus poly(A) tail lengthening depends on the initial length upon infection and that the minimum length to initiate lengthening may lie between 5 and 9 nucleotides. By mutagenesis analysis, it was found that (i) the hexamer AGUAAA and poly(A) tail are two important elements responsible for synthesis of the coronavirus poly(A) tail and may function in concert to accomplish polyadenylation and (ii) the function of the hexamer AGUAAA in coronaviral polyadenylation is position dependent. Based on these findings, we propose a process for how the coronaviral poly(A) tail is synthesized and undergoes variation. Our results provide the first genetic evidence to gain insight into coronaviral polyadenylation.

Peng Y-H, Lin C-H, Lin C-N, Lo C-Y, Tsai T-L, Wu H-Y (2016) Characterization of the Role of Hexamer AGUAAA and Poly(A) Tail in Coronavirus Polyadenylation. PLoS ONE 11(10): e0165077

Re: Why does the SARS-Cov2 genome end in aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa? (2020)

#60
post #33

File formats are really easy to figure out and are a big advantage for moving data around. Even without an academic theory, pretty much everyone in software starts to figure out the same tricks as soon as reliable transmission becomes a goal. I assume that at least one reason for this is that genomes are data, data likes to live in structured formats, and file terminators are more reliable for biology to process than…

So something to keep in mind when looking at biological systems, and especially when looking at genomics - evolution doesn't actually have a master plan or agency, it's just drift and reproduction. There's a lot of reuse and a lot of parsimony that can look elegant, but there's no 'design' process of evolution - it's a pile of things that looked enough like other stuff that over time with some tweaks they could take on dual roles. There's also no separation of concerns - DNA is a molecule, and it's acted upon by other molecules following the same rules of chemical and quantum interactions that affect everything else. Certain RNA sequences aren't transcoded but rather fold into functional molecules and enzymes, and protein folding and subsequent structure and function is affected by how fast the RNA is transcribed, which is affected by the population of available tRNA molecules. Genomics only looks like information - it's still chemistry.
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