Talk:Messenger RNA

mRNA structure

Don't have time now, but mRNA in eukaryotes should be circular because if eIF4 class cap recognition proteins and PABPI.

Polyadenylation step could be more detailed

It could be detailed, but the already existing article (see http://en.wikipedia.org/wiki/Polyadenylation) must be partially corrected by the following indications :

The present description and the drawing of the reaction are wrong :

the poly(A) polymerase (PAP), the CSPF, and the poly(A) tail regulator PABPN1 (the first PABPN1 bound to the 11 AMP residues added), must be interacting as a tripartite complex during the entire reaction of polyadenylation, since the processivity (that is the ability to add an AMP per catalytic cycle without dissociating from the 3'OH of the RNA between each catalytic cycle) of mammalian PAP relies on this tripartite complex.

The current model of termination for the mammalian polyadenylation reaction suggests that the PAPBN1/poly(A)250-300 tail forms a globular shaped RNP (ribonucleoparticule) of about 20 nm in diameter, and that this could sterically disrupt the tripartite complex mentionned above, leading to a change from processive to distributive activity of PAP, and therefore termination.

The drawing should in fact show the CPSF/PAP/firstPABPN1 complex at the site of cleavage, and as the poly(A) tail grows, the number of AMP residues increase, but the 3'OH end of the RNA always stays in contact with PAP located near CPSF, leading to the formation of a buckle of poly(A), PABPN1 proteins bound to it.

The current drawing shows PAP at the end of the RNA, with no interaction with CPSF or PABPN1 : in this case, PAP couldn't be able to add the poly(A) tail with real efficiency.

For references, type Elmar Wahle in pubmed, or see :

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=7852352&query_hl=3&itool=pubmed_DocSum

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=8440247&query_hl=3&itool=pubmed_DocSum

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=1878970&query_hl=3&itool=pubmed_DocSum

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=12853485&query_hl=3&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=11994003&query_hl=3&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=10731412&query_hl=3&itool=pubmed_docsum

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=9061026&query_hl=3&itool=pubmed_DocSum

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=9175430&query_hl=3&itool=pubmed_DocSum

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=8428968&query_hl=3&itool=pubmed_DocSum

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=1993684&query_hl=3&itool=pubmed_DocSum

Is there a place I can go to learn about Messenger RNA?

Is there a place I can go to learn about Messenger RNA? I would need a PhD to understand this article, and I was just trying to get a handle on what Messenger RNA actually is and does. I was hoping to find that here. 73.6.96.168 (talk) 18:42, 18 September 2020 (UTC)

In very short, messenger RNA is an intermediate piece of genetic information that is used by the cell to synthetize a protein. Hope it helps! Manudouz (talk) 18:05, 19 September 2020 (UTC)

You do not need a PhD to understand this article! It has probably been written by undergraduates. John2o2o2o (talk) 10:31, 3 October 2020 (UTC)

Poor and misleading wording

This line: "mRNA is created during the process of transcription, where an enzyme (RNA polymerase) converts the gene into primary transcript mRNA (also known as pre-mRNA)."

Is plain wrong and very misleading. RNA polymerase does not convert genes to mRNA. The nuclear DNA on which genes are coded is not altered at all. A section of it is copied - transcribed - as a piece of mRNA by RNA polymerase.

This article has much clearer wording: https://en.wikipedia.org/wiki/RNA_polymerase

I suggest that it is used to improve this article. John2o2o2o (talk) 10:31, 3 October 2020 (UTC)

History of mRNA as given conflicts with contents of cited article

It looks like the current sentence in the article on the history of mRNA is derived from these edits in 2014 and 2015 by users LilyKitty, Graehare, and Johnrayphd.

Unfortunately, the cited article (which was added later) indicates that the actual history was rather different. I propose to reword the sentence on the history of mRNA to the following:

The possibility of the existence of mRNA first came to Sydney Brenner and Francis Crick on 15 April 1960 at King's College, Cambridge, while François Jacob was telling them about recent findings of an experiment conducted by Arthur Pardee, himself, and Jacques Monod (later known as the PaJaMo experiment). That summer, the existence of mRNA was demonstrated in an experiment conducted by Brenner, Jacob, and Matthew Meselson at the California Institute of Technology, and that fall, Jacob and Monod coined the name "messenger RNA" and developed the first theoretical framework. In February 1961, James Watson revealed that his research group was just behind them with an experiment in the same general direction and asked them to delay publication of their research. As a result, the Brenner and Watson articles were published simultaneously in Nature in May 1961, while that same month, Jacob and Monod published their theoretical framework for mRNA in the Journal of Molecular Biology.

If no one objects, I plan to insert this text in a few weeks. --Coolcaesar (talk) 20:02, 7 June 2021 (UTC)

Hearing no objections, I'm going ahead. --Coolcaesar (talk) 18:57, 15 June 2021 (UTC)

Dr Robert Malone

Why was Dr Robert Malone, the inventor of mRNA vaccines, removed from the article? Does it have anything to do with him coming out publicly saying he had grave concerns about it, 5 days before his name was removed? Is he the inventor or not? Internet searches seem to indicate that he is. Why are facts being removed from WikiPedia? I would be happy to discuss with the person who claims that Mr Malone didn't invent mRNA technology, maybe we can have a good discussion. The sentence that was removed: "mRNA was invented by Dr. Robert Malone."

139.216.142.156 (talk) 23:53, 29 June 2021 (UTC)

mRNA is not a human invention, sorry. — kashmīrī ^TALK 18:41, 30 June 2021 (UTC)

The statement in the article currently says "The idea of mRNA was first conceived by Sydney Brenner and Francis Crick on 15 April 1960 at King's College, Cambridge..". Since you made the claim that "mRNA is not a human invention" (agreed) please remove this line of text immediately. Your later argument about a patent war over mRNA vaccines should be justification to remove any claimant. 174.250.4.6 (talk) 14:17, 4 July 2021 (UTC)

The event described is Crick coming up with the idea of how such a thing could work. Just as previously they had discovered the structure and function of DNA just a few . mRNA is one of the basic components of life and, along with DNA, method of transmitting biological information. RMA actually predates DNA, as well as, of course, life itself. So it is obvious that nothing could be more absurd than to call it a human invention, humans and life could not exist at all without mRNA. The mRNA in the mRNA vaccine itself isn't a human invention either, covid 19 is an RNA virus that relies in mRNA (rather than DNA) as it's fundamental information carrying protein. When infected with COVID 19, one of the things that happens is that immune cells in your body will "eat" the virus, and break it down until its fundamental proteins, one of which is, of course, is mRNA. The immune cells then travel to the lymph nodes and begin using that mRNA to produce the various antigens of the virus, and present them to the T-Cells (the "killer cells" of the immune system) so that the T-Cells can begin building antibodies and recognize and rapidly destroy the pathogen in the future.

In a normal vaccine, dead or inactive virus cells would be injected into the body to achieve the above without having to go through an infection. In an mRNA vaccine, instead, just the mRNA itself is injected, the immune cells "eat" the mRNA itself and do the above, without having to go through the process of breaking down the virus into its constituent proteins. The mRNA itself is not anything new or novel, as during a normal covid infection the exact same mRNA would at some point be isolated by the immune cells, it is just the viruses own mRNA which is a fundamental part of the pathogen. The only real trick is wrapping the mRNA up so that it can survive the trip into the body and be picked up by the immune cells, as mRNA is usually rather fragile and would degrade. They accomplish this by wrapping it in a nanolipid, which eventually degrades within a few days, allowing the immune cells to interact with the mRNA after eating it. None of the above would work if the nanolipid did not degrade, the mRNA itself wouldn't be able to interact with anything.

Why was the above done with the COVID 19 vaccine?Because building a vaccine through this process is much faster than traditional vaccine, and it was an unprecedented emergency under which every single second mattered. An mRNA vaccine prototype can technically be produced in a matter of weeks, VS months with the traditional method. That's months where you can be going through the testing process rather than still be stuck prototyping. That's hundreds of thousands of lives. If it had been an unmitigated disaster as is claimed by denialists, it would've been immediately apparent in the testing, and it would've been canned and all efforts probably would've gone into readying the Johnson and Johnson vaccine instead. But it wasn't a failure and the mRNA vaccines were able to be authorized first. And they are still preferable because it turns out the Johnson and Johnson vaccine actually does have some side effects not present in the mRNA vaccine. If the MRNA vaccines had been a failure, the J&J vaccine would still be preferable to getting COVID. But as they were not, why wouldn't you choose the safer alternative? And vaccine skeptics who cite MRNA as a justification for their denial, why don't they take the J&J, which didn't utilize any novel methods? If the side effects of mRNA (ie a fundamental constituent of virtually all life on earth) are being evilly hidden, you can still get vaccinated without it. They act as though this method is being forced on them. It's not, the mRNA ones are just generally considered safer. But if it were the case that mRNA were actually dangerous and this were being covered up, this is utterly irrelevant to the efficacy of the J&J one, so go get that. It is only considered less safe in comparison to lies, so clearly it yes the safest one by that logic. And ofc all options are safer than COVID.

In reality the specific method the vaccine uses isn't truly relevant to their denial, if it were not this, they would seize on something else too scaremonger. Fundamentally, their thought process is broken, and they will refuse to accept any answer they do not want to hear. What they want to hear about the vaccine, is the the evil librulz are trying to poison them, and they construct their reality around that desired belief and ignore contradictory information. There is just something about vaccination as a medical treatment that tends to drive certain people stark raving barking at the moon mad, always has been. Even when Mather first proposed smallpox inoculation in the colonial era, he was met with considerable contempt, incredulity, and ridicule, until the Smallpox pandemic finished sweeping through and there were heaps of dead among the uninoculated and few among his. And inoculation actually was a very risky procedure that had a high chance of death - still much safer than smallpox, but orders of magnitude more dangerous than any existing modern vaccine. But of course people were appalled at the idea of such a treatment, what you can die of it, I'll just take my chances with the smallpox hahaha! And the people who made that decision wound up dead in droves, they chose to disregard a preventative treatment with small risk to gamble at just avoiding a pathogen with large risk. And it was an incredibly foolish gamble as the death tally soon made apparent, there were many a mournful parent who wished they had gotten their family inoculated. And the same logic applies with vaccines, regardless of how safe they are made, the existence of any side effects at all is blown out of all proportion, and people go online and tell each other ghost stories making up purely fictional accounts of how awful this treatment supposedly is, and hahaha I'll just gamble with the virus. If that were the case, why don't we just inject you with the virus straight out? If we had such a policy en masse, there would be millions of dead. Clearly, they do not actually intend to get the virus. They wish to gamble and be a lucky one and avoid all the supposed harm from all options entirely. They do so while exposing themselves to far higher risk, but to ignorant people a gamble is always preferable to a certain, but small harm. This behavior is incredibly selfish of course, these people also like to talk about "herd immunity", but such a thing cannot be achieved through natural spread. Either nearly everyone has to get the vaccine, or nearly everyone has to be artificially infected - natural spread will always die out before reaching a rate at which herd immunity exists. If the option were between the vaccine and artificial infection, the calculus would be obvious. But these people intend on gambling, being lucky and avoiding the natural spread, and thus remaining a future vector for possible future flare ups of new versions of the virus. Every unvaccinated who doesn't get the virus, is a resoivoir for its re-emergence, herd immunity is impossible while the "lucky" exist in any large numbers. 2601:140:8900:61D0:2134:A70C:463F:9009 (talk) 23:34, 7 September 2021 (UTC)

Vaccines are, just saying. It might be reworded. HighInBC ^{Need help? Just ask.} 11:29, 1 July 2021 (UTC)

HighInBC, There is some sort of patent war going on. Malone seems to claim IP rights to mRNA vaccines (not sure there are grounds to it). He is featured on antivax sites and in fringe media speaking against mRNA vaccines, calling them untested, etc. He recently complained on Twitter that his LinkedIn account was deleted. I'd be wary of Wikipedia giving a platform to such claims without strong sourcing. — kashmīrī ^TALK 11:49, 1 July 2021 (UTC)

Thank you. This is what I get for commenting on something I barely know anything about. I withdraw my comment. HighInBC ^{Need help? Just ask.} 11:51, 1 July 2021 (UTC)

Yeah, me using Google mainly and reading headlines, and articles like this one raise a red flag for me. I also glanced through the original 1989 article[1] in which Malone and two other academics indeed proposed mRNA as a possible therapeutic method, possibly for the first time. But this does not make them "inventors of mRNA vaccines" as some (incl. Malone) claim - even the word "vaccine" does not appear even once in the text. Only in the last sentence the authors speculate about the possible use of this mRNA transfection technique in developing new gene therapy drugs. — kashmīrī ^TALK 12:05, 1 July 2021 (UTC)

I first came a number of days ago to add “Malone is the inventor of mRNA vaccine…” (because that’s his claim on Twitter) — but now having researched it, I can see that he is NOT; but he did do important work along the way. In comparison, if mRNA were a building, Malone had the idea and knowledge to add windows. He (and his party) added one contribution out of a dozen, to get us to where we are today. I think a history of mRNA should be spelled out - to not only give Malone his proper place - but to correct misinformation about him, (that he’s the inventor), and to stop people trying to edit that into the article going forward. (He keeps claiming he’s been edited out of Wikipedia, driving people here). My two cents. It’s protected so I can’t edit it for now. 198.48.187.109 (talk) 18:07, 1 July 2021 (UTC)

That's how science works. People add bits and pieces of research for years, until one day someone makes them into a marketable product. Malone found out that it is possible to transfect cells using mRNA encapsulated in nanolipids. Others came up with RNA encapsulation in amine-containing polymers; still others went for conjugation of a bioactive ligand in the RNA that enables it to enter the target cell. Recently, BioNTech and Moderna chose the nanolipid method to develop their vaccine. This hardly makes Malone the vaccine "inventor" – especially given the fact that the first discussion about employing mRNA technology in vaccines was dated to several years after Malone's initial publication[2]. — kashmīrī ^TALK 19:42, 1 July 2021 (UTC)

How are you justifying spelling out that the process which BioNTech and Moderna chose to use is the one he discovered while simultaneously justifying his removal from the page? He is a contributor to the process chosen for this technology and it only makes it more suspect when people come here to look for him after he states something controversial - especially his removal from the page. Cite why it's controversial or disprove/clarify what he claims, note the conflict of interest, etc. Otherwise it's just fueling the conspiratorial dumpster fire to just simply wipe his name. Re: your comment about the word "vaccine" not being included in the paper: the word "vaccine" is hardly mentioned on this page itself, so why not add Dr. Malone to the page elsewhere for his particular contribution to the underlying technology and delineate specifically that he is not involved in these vaccines? Also, the article you cite specifically says "using RNA as a drug" - is a vaccine not a drug? I think it's a distinction without a difference. If this sort of "wiping" becomes more and more widespread, the people who most need this information to be accurate, and not just queried for its omissions, to help them dispel any wild notions that pop up in the daily twitter cycle, will just trust it less and less and make discussions like this virtually moot. 94.140.9.184 (talk) 07:08, 6 July 2021 (UTC)

It's not our role to disprove unfounded claims. Simply, we publish only what reliable sources confirm. No reliable source states that the guy invented mRNA vaccines. To the contrary – it's quite clear he did not. He was simply a member of the team that first demonstrated that nanolipids are a feasible vector for RNA transfection. Only this, and as much as this. Yet demonstrating that oil burns doesn't make one an inventor of the diesel engine. — kashmīrī ^TALK 07:33, 6 July 2021 (UTC)

That analogy doesn't parse well; it's more like: "we've shown that oil can be manipulated into gasoline which can then be used as fuel" but not specifically mass-producing that fuel or specifying the engine in which it will be used. Your own source claims that they discovered the process/developed a technique whereby mRNA transfection could be used as a drug. Someone else took that idea and said: hey we'll use this already-researched technology for a specific purpose, mass-produce it and label it as a vaccine. Removing him because they didn't specify "vaccine" and instead used "drug" is kind of specious, especially when it is debatable whether this technology is strictly a vaccine (seemingly your claim) or a wide-application gene-based therapy; "drug" then would be the most suitable term in their paper as the technology itself blurs this distinction. Edits to reflect this for clarity should be considered based on what is being claimed to be important here. If I invent a technology or technique and say "this technology has many different uses" and someone else uses my technology to develop one of its particular uses, I still invented the technology. Not sure how that is debatable or is a reasonable reason for his deletion. 94.140.9.151 (talk) 17:32, 6 July 2021 (UTC)

Disagree. They simply demonstrated that nanolipids can be used as a vector for cell transfection with RNA. They did not invent nanolipids nor discovered mRNA, nor were the first ones to transfect cells using mRNA. They also did not come up any practical use of their discovery, did not develop any mRNA-based drug, vaccine, etc. They just demonstrated the feasibility of one of several methods to transfect cells. And it so happened that someone made a practical use of that method 20 years later. They deserve some credit, but only for what they did and not for what they claim today when big money is at stake due to other people's work. — kashmīrī ^TALK 18:34, 6 July 2021 (UTC)

Ok. That is all fair. Undelete him and credit him and the two others where credit is due. Distance him from the vaccine section, as that is the false claim which led to his deletion, and then we can all hopefully move on towards not making such damaging deletions in the future. Or was his initial inclusion to the page illegitimate? I feel that we should address whether his name was on here erroneously or illegitimately before he was removed. Or will no damage control be considered? The vacuum left here will just be filled by some other platform. 94.140.9.151 (talk) 21:44, 6 July 2021 (UTC)

"when people come here to look for him after he states something controversial"

... So ... because he's falsely claiming to be the inventor of the vaccine, and because he's using that stolen glory to push dubious claims ... we should call attention to him?

No. That is not a good idea. There's no need to reward attention-seeking lies. It's not Wikipedia's job to help him get a book deal, or whatever it is he's angling for. We only need to cover what the RS attach significance to, we don't have to cover people who try to attach significance to themselves. ApLundell (talk) 18:39, 6 July 2021 (UTC)

Did he or did he not develop the method -> credit him for it if so. I don't give a damn about him personally but the removal of him from this page has caused quite a few people to feel that his statements are validated about vaccines - and that is on wikipedia - not his making the false/misleading claims. Literally no one here is asking for false claims to be published, but we should publish the outline of the work that kashmiri cited[3] in the comment above. If it does have legitimacy as part of the foundational steps towards the development of these vaccines then by your own definitions one shouldn't be interfering by deleting him from an ancillary part of the page. Don't even put him near the vaccine section for all anyone cares. What I'm saying is that the deletion of his name has brought people here and that is validating notions of the conspiracy against him. If you don't want him to get "a book deal" or whatever - just publish what is true and reliable. That isn't "rewarding" anyone - that isn't the purpose of this site, as several people keep trying to reexplain. In the same vein you don't get to punish people by deleting their valid contributions to the subject matter if later on they make any specious or ridiculous claims for suspected grifting purposes. Especially without any evidence of that claim besides also-dubious hearsay. Anyway, if you can't see the damage that it does to vaccine legitimacy with the memory-holing activity, I'm not sure what goal is being attempting here. 94.140.9.151 (talk) 21:44, 6 July 2021 (UTC)

There are no names mentioned in the Applications section, and that's for the better, because it is only a concise summary of RNA therapeutics. The right place to mention Malone's work is in RNA therapeutics, not here. — kashmīrī ^TALK 22:22, 6 July 2021 (UTC)

We really don't care what "brought people where". We're not here to react to what's happening on social media.

You understand that listing out everyone who ever contributed to the field would not be a normal thing to do, right? It would be weird. (And listing a single name would be even weirder!) You're asking Wikipedia to make an exception and do something out of the ordinary, and the only reason you've given is because people will "expect" it because this guy is making noise on social media. ApLundell (talk) 23:12, 6 July 2021 (UTC)

Seems pretty normal to list who invented something. Clearly wikipedia wants to move into the post-fact age, where everything's an opinion. Clearly they were told to do this by the same people who runs the Covid show. Iskube (talk) 15:50, 21 July 2021 (UTC)

But is it normal to list a man who calls himself the inventor, but really has a different, more minor role? ApLundell (talk) 17:07, 21 July 2021 (UTC)

Therapeutic

I want to add this to the Applications section. Placing here for discussion:

Overcoming these challenges, mRNA as a therapeutic was first put forward in 1989 - “after the development of a broadly applicable in vitro transfection technique” — Preceding unsigned comment added by 198.48.187.109 (talk • contribs) 11:14, 1 July 2021 (UTC)

I've restored your edit, I think it's factual and non-controversial. Thank you for using the Talk page to build consensus. — kashmīrī ^TALK 13:44, 1 July 2021 (UTC)