Genome Wrapping and the coding level above viral RNA
Here is my quest to understand the coronavirus. I will sum up the story I began with my coronavirus puzzles plus add a lot more. I have asked Rhiju a bunch of questions and brought back the spoils.
Coronavirus - Solenoid
Coronavirus is an RNA virus.
Image of the coronavirus from WHO:
What is COVID-19 All You Need To Know “Corona Virus”
Cynwulf28 puzzle Solenoid as when screenshot halfway in between target and native looks just like the covid19 when bound up inside the viral capsid as in WHO’s image.
Eli: I wonder if these nucleoproteins are binding anywhere specific sequence wise in the RNA? Plus if the RNA is really like a flat circle in a 3D ball of viral protein?
Rhiju: I haven’t been able to find good studies on what RNA motifs the nucleocapsid (‘N protein’) binds to perhaps that something players could help figure out!
eli: Yes. I recall reading about it earlier somewhere in relation to another virus
rhiju: yes, even in ebola it’s not clear how the RNA wraps around (or inside) the nucleocapsid protein filament. Fascinating question.
eli: Oh. It kind of also reminds me of tobacco mosaic virus protein capsid. While that is a spirally wrapping around the RNA. (In a tube) And the above is a 3D wrapping. (Sphere)
Coronavirus - From solenoid to yarn ball
I was wondering about if the corona virus really was folded up like a flat circle (2D) in a ball of viral protein (3D) as in the WHO image.
Molecular Landscapes by David S. Goodsell
I was really happy when I found David Goodsell’s Covid-19 image. His image gave me an answer to what I was wondering about in relation to how the RNA was packed up inside the viral capsid. Because he always makes his images based on views on actual molecules. (The article linked under the picture holds reference to the papers from which it is based on.) So the RNA strand both touches up with the capsid, but the RNA strands also line up against each other when more inside the capsid.
The viral RNA is much more bundled up as a yarn ball. With the one RNA curl lining up to the next one and parts of them touching the viral shell. Just like yarn strings lying close to each other, in a yarn ball.
In a ball of yarn, one can get action if one grabs the outer tail. Whereas threads in lower layers are not available for interaction.
eli: I wonder, which of the tails of the virus is the outer tail in the RNA yarn ball? The 5’ or the 3’? Or both, like in a yarn ball?
rhiju: Yea, I’ve been wondering that too! There’s some evidence that the 5’ and 3’ ends interact at some point in the virion life cycle, maybe throughout.
eli: Lol and sigh. Viral circle of doom.
rhiju: check these papers out:
Sequence Motifs Involved in the Regulation of Discontinuous Coronavirus Subgenomic RNA Synthesis
Characterization of the RNA Components of a Putative Molecular Switch in the 3′ Untranslated Region of the Murine Coronavirus Genome
What is happening - RNA histones?
What you didn’t know about your RNA, by DNews
I kind of get the nucleoproteins for the corona RNA. While it does have a function of attracting and keeping the viral capsid in place, it is also kind of RNA histones.
Nucleoprotein wrapping around the corona RNA:
Molecular Landscapes by David S. Goodsell
I think I have never before seen RNA bundled up in like sized and similar threads.
A viral chromosome/plasmid
Rhiju: “RNA histones”. Yes!!
eli: Lol. Is there really such a thing?
My search engine suggest I search for “DNA histones” when I try “RNA histones”
rhiju: [regarding RNA histones, check out this paper:
RNA epigenetics - A layer above RNA
Eli: That is amazing. So nucleoprotein positions determine the splicing positions, depending on the sequence like UUUUU in mRNAs.
I have been searching on and found other examples and I’m now thinking that RNA just like DNA can have epigenetics.
Epigenetics - An introduction By Armando Hasudungan
Just one example. Viral RNA can have methylations just like DNA. And it can matter to how the mRNA gets read by the ribosome. Plus how well it is translated.
Which makes me wonder if we can methylate corona mRNA to hell?
Here is a paper on viral epigenetics. It is most about DNA epigenetics, but it is starting to mention the phenomenon in RNA also:https://www.ncbi.nlm.nih.gov/pubmed/25421681/ I only have access to the abstract.
@rhiju, another thing that makes me think that the nucleoproteins in coronavirus has a role in the very neat wound up RNA, is that I have read in Wikipedia under coronavirus, that coronaviruses have the longest viral RNA genomes. (26 to 32 kilobaser, or 26000 to 32000 bases)
While I’m aware that the viral capsid proteins have a role in packing the RNA tight, I just can’t imagine a yarn ball getting made by yarn being wound from the outside and in.
Hence I think that the nucleoproteins play a role in the packaging.
rhiju: there is a preprint on SARS-CoV-2 methylations — let me dig it out
eli: Thx for the corona methylation paper! Lol on this phrase “DNA nanoball”. I say RNA nanoball
@rhiju, if these “RNA histones” are different from human histones, then they may be useful as a target, to prevent the RNA from assembling in a ball. From what I understand histones don’t mutate a lot, so it may be a more stable target to attack.
The paper was a most interesting read. Especially cool that they found a connection with the most chemically modified mRNA to have the shortest polyA tails.
Afterthought, perhaps corona RNA has some chemical modifications of a type that is not used in human and bacterial cells? (we don’t want to harm our microbiome) Then those may be usable as a target.