Thread by @pleunipennings

I like doing science to take my mind off of the pandemic. Plus, I need to prep my genetics class for next week. And against advice from smart people, I will talk to my students about coronavirus to remind them of “normal” genetics. (thread) 1/

2/ A lot of this info is from this video: @brittaspen @hhmi
h/t @vscooper and @elsanchez09
And from viralzone.expasy.org/30?outline=all…

3/ So let’s start at the beginning, which for a virus is the moment it enters a cell.
Viruses don't have cells, but need cells to do anything!
The viral particle of SARS-CoV2 contains a single, positive strand RNA genome of about 30,000 nucleotides.

4/ Single stranded means that it is not basepaired. Our own genome (as humans) consists of DNA and it is double stranded – every A is paired with a T and every G with a C. Not so in single stranded virus genomes.
Double-stranded RNA viruses also exist by the way.

5/ The SARS-CoV2 RNA is called “positive strand” or “positive sense” or “plus sense” because it can be translated immediately. Once it enters a human cell, our (human) ribosome machinery starts translating the RNA. Not very smart, human cell!

6/ Translation mostly works following the normal rules. Starting from a start codon and going until it hits a stop codon. Pretty simple huh?

7/ You remember the start codon? AUG. That’s where it starts.
And the stop codons? UAA, UGA, UAG (Nice mnemonic for those: U Are Annoying, U Go Away and U Are Gone).

8/ You can got to genbank and look at a SARS-CoV2 genome ncbi.nlm.nih.gov/nuccore/MN9089…
And copy the nucleotides into this translation tool: web.expasy.org/translate/

9/ You should see, near the beginning of the genome, a large open reading frame (ORF), here recognizable as a big block of pink in the image (in this case in Frame 2) – it results in a string of 4382 Amino Acids.

10/ Now here is a really great (nasty) virus trick.
This string of 4382 amino acids doesn't just make one protein, it makes 11!
It is a so called "polyprotein" that can be cut up in the proper proteins.

11/ Polyproteins are used by many viruses.
This polyprotein (SARS-CoV2 Orf1a) is cleaved (or cut) into the actual proteins, which are called
ns1
ns2
PLpro (a protease)
ns4
3CL (also a protease),
ns5
ns6
ns7
ns8
ns9
ns11.

12/ You may wonder what enzyme does the cleaving of the polyprotein? As I understand it, PL Pro (papain-like protease) and 3CL (3C-like protease) cut the polyprotein while they are still part of it. It's called “autoproteolytic cleavage.” No need to remember that word ;-)

13/ OK, so to summarize this bit: the SARS-CoV2 RNA is translated by our ribosome, from a start to a stop codon, resulting in a polyprotein that cuts itself into 11 proteins.

But that is just the beginning! More tomorrow about the virus tricks us into ignoring a stop sign.