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How does RNA know where to go in the city of the cell? Using cellular ZIP codes and postal carrier routes

22 Comments
By Matthew Taliaferro

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The inner workings of DNA and human biology in general are extremely complicated and science isn't even anywhere near close to fully understanding how and why things happen in the body.

That reason would apply to every other kind of medical intervention, do you also abstain from using any kind of medicine, medical procedure, etc? Because all are used even when the physiological processes of the body are complicated and not anywhere close to be fully understood as well.

Artificially messing with RNA and DNA could have unforeseen consequences.

And extremely beneficial uses as well, studying something can mean making the benefits greatly outweigh the risks, again the same as every other kind of therapy.

Something wrong with the old zip codes?

As they clearly explain in the article, the 'old' ones are not complete, so in order to direct the molecules to the specific sites the researchers intend, they need to find new ones and how they are used by different cells.

1 ( +7 / -6 )

I choose the ones and I won't and refrain from those I don't.

My point remains the reasons you said make you refrain from using this specific kind of therapy would also make you refuse every other medical intervention as well, meaning that you yourself are demonstrating it is not a rational position to take by ignoring it for those that you choose.

And imposing consequences is a type of coercion which the Nuremberg code specifically said that the government can not do.

No, it does not, because the Nuremberg code is not what regulates the ethical use of medical procedures, the same way that the Chemical Weapons Convention is not the one that regulates how to properly use cleaning products.

Once again, when you openly choose to completely ignore the reasons you give but only for some medical treatments you make obvious those are not valid reasons even for yourself, at much they are a excuse you apply by using double standards to justify the actual reasons because they are illogical.

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Well, the mitochondria have their own genome, which encode several proteins involved in energy production.

If the purpose is to modify energy production it would have no importance from which genome comes the coding for the proteins, the important part is that the RNA still have to be delivered to the mitochondria to fulfill that role.

Also, proteins themselves have "zip codes" that direct them to specific locations.

But as discussed in the article it is not as efficient to move proteins as it is to move the RNA, the amount of energy needed for proteins to reach a specific location is much greater, so as the example of the mitochondria it can be simply much more efficient to deliver RNA instead.

Fine, allow Big Pharma to tinker with your DNA as much as you like.

How does using RNA means "thinkering with your DNA"? you understand it is a completely different thing, right?

But understand that a person has an absolute right to accept or decline medical interventions on their physical body.

Which is why I made the question to you, the reason you give would make every other kind of medical intervention equally unacceptable, so you refuse all of them, right?

If not, then you are accepting the reason you gave is not valid even for yourself and instead are using double standards.

0 ( +6 / -6 )

Except for the RNA that is made in the mitochondria...

What "except" is that? the whole point of the article is to elucidate how to reach a space (for example the mitocondria) obviously that means introducing something that is not there in the first place to cause a benefit.

If an article talks about how to deliver certain therapeutic protein to the brain there is no point in saying "except that there are already proteins on the brain" obviously those proteins would not be the target of the research and the health problem is still present even if they are on the target destination from the beginning.

0 ( +6 / -6 )

The article is giving the impression that all DNA in cell is stored in the nucleus:

No, it is simply making a simple explanation of the process, without ever saying this only happens in the nucleus, that would make no sense since this process also happens on prokaryotes.

I just wanted to add some relevant information that I thought was missing from the article, regarding the natural cellular processes.

While making a quote of a comment that is much more closely related to the content. You don't want people thining you are talking about a previous comment? that would be very easy, don't quote it in the first place.

You also understand that if you are free of adding information about the article so are other people by doing the same for your comment, right? What is the point on saying you want to write something and then telling other people should not do the same?

he work discussed in the article does have potential, but I certainly would recommend avoiding any treatment based on RNA until what happened with the current mRNA products is addressed openly and people are held accountable..

Accountable for what? the fast development of safe and effective vaccines that have helped saving millions of lives and that the scientific and medical consensus say is one of the best accomplishments that could be made thanks to medical science?

If anybody should be made accountable that would be the people that choose to repeat false imformation to mislead others trying to exaggerate risks while pretending the pandemic was not a huge public health problem.

0 ( +6 / -6 )

At last, some truth on RNA. Essential reading for all who are interested in the covid vaccine

the COVID-19 pandemic has shown the power and promise of this molecule to the world at large

0 ( +3 / -3 )

That is what this article is all about, are you commenting without reading it?

I did read the article. And I already said the research has great potential, but I don't see how it could be of any use for the mRNA Covid vaccines.

There is nothing strange about localization signals that let the mRNA reach specific spaces, membranes or organelles inside the cell can improve this function even more.

For some mRNAs, I agree. But for the Covid mRNA vaccines, how? You claimed they would be of great benefit. Based on what?

0 ( +2 / -2 )

Similarly, proteins devoted to energy production for the cell are most functional not when they are confined to the nucleus but when they are in the cell’s power plant, the mitochondria, surrounded by the raw materials and accessories needed for their job.

Well, the mitochondria have their own genome, which encode several proteins involved in energy production.

Also, proteins themselves have "zip codes" that direct them to specific locations.

-1 ( +4 / -5 )

At last, some truth on RNA. Essential reading for all who are interested in the covid vaccine

Yeah, but those mRNA products, with their pseudouridines and lipid nanoparticles, are not your typical mRNA. And I don't think the article's main topic, the "ZIP code" on the RNA molecule, is of any relevance to the Covid products.

-1 ( +2 / -3 )

Yeah, but those mRNA products, with their pseudouridines and lipid nanoparticles, are not your typical mRNA. And I don't think the article's main topic, the "ZIP code" on the RNA molecule, is of any relevance to the Covid products.

Which makes it strange that you were the one that began discussing them, also mRNA can be directed by signaling so if there is any advantage to directing vaccines (including covid vaccines) to specific intracellular places then this research would still be very beneficial.

-1 ( +2 / -3 )

Yeah, but those mRNA products, with their pseudouridines and lipid nanoparticles, are not your typical mRNA. And I don't think the article's main topic, the "ZIP code" on the RNA molecule, is of any relevance to the Covid products.

Which makes it strange that you were the one that began discussing them,

No, that is incorrect.

They are mentioned in the 2nd sentence of the article, and directly or indirectly mentioned by Bronco and you before I ever mentioned them.

Also, I am simply pointing some important differences between the mRNA vaccines and the topic of this article. I was responding to Elvis' "Essential reading for all who are interested in the covid vaccine".

Nothing at all strange about my comment....

-1 ( +2 / -3 )

also mRNA can be directed by signaling so if there is any advantage to directing vaccines (including covid vaccines) to specific intracellular places then this research would still be very beneficial.

But for covid vaccines, the encoded protein is targeted to the external membrane. How would these "ZIP codes" on the mRNA be of any use. They should instead focus on the lipid nanoparticles, trying to prevent them from spreading throughout the body and delivering their payload to any cell they bump into.

-1 ( +2 / -3 )

No, that is incorrect.

You wrote that the concept is of no relevant to covid vaccines, even after you yourself mentioned them in your own comment, that means it is not incorrect, you are complaining about other people talking about something you yourself did first.

Also, I am simply pointing some important differences between the mRNA vaccines and the topic of this article. I was responding to Elvis' "Essential reading for all who are interested in the covid vaccine".

And then saying this is irrelevant to the conversation, even when you are doing the same.

But for covid vaccines, the encoded protein is targeted to the external membrane. 

The protein is meant to REACH the external membrane, not to be produced or processed there, activation of the intracellular pathway of immune response is an important part of the process that gives an advantage over simple protein based vaccines, which means there is plenty of room to be improved by making the RNA to be located intracellularly as in the infection.

 They should instead focus on the lipid nanoparticles, trying to prevent them from spreading throughout the body and delivering their payload to any cell they bump into.

Since there technology have already allowed for a much safer way to expose the body to the antigen compared with the much more risky natural infection this is of little value, the benefits of modifying intracellular localization of RNA would have a much higher impact than just improving a safety profile that is already high enough.

Right on the money.

As explained this comment makes invalid assumptions that ignore the very important evidence of the intracellular pathway the mRNA follows that improve vaccine efficacy, basic knowledge of mRNA vaccines should be enough to avoid this mistake.

-1 ( +2 / -3 )

But for covid vaccines, the encoded protein is targeted to the external membrane. 

The protein is meant to REACH the external membrane, not to be produced or processed there,

Yes, and once the lipid nanoparticle delivers the mRNA into the cell, how can a "ZIP code" help, where does the mRNA need to go?

-1 ( +2 / -3 )

Yes, and once the lipid nanoparticle delivers the mRNA into the cell, how can a "ZIP code" help, where does the mRNA need to go?

That is what this article is all about, are you commenting without reading it?

For a handful of mRNAs – or RNA sequences coding for specific proteins – researchers have an idea about how they’re transported. They often contain a particular string of nucleotides, the chemical building blocks that make up RNA, that tell cells about their desired destination. These sequences of nucleotides, or what scientists refer to as RNA “ZIP codes,” are recognized by proteins that act like mail carriers and deliver the RNAs to where they are supposed to go.

The whole point is that intracellular localization is important for the functions of the mRNA, and activation of the intracellular pathway of innate immunity is already known to be one of the reasons mRNA vaccines are more effective than simple protein or inactivated virus based vaccines. There is nothing strange about localization signals that let the mRNA reach specific spaces, membranes or organelles inside the cell can improve this function even more. After all viruses have specialized strategies to avoid their RNA to reach certain spaces precisely to avoid this activation.

-1 ( +2 / -3 )

I did read the article. And I already said the research has great potential, but I don't see how it could be of any use for the mRNA Covid vaccines.

As is often the case, people can explain things to you, but nobody can understand things for you.

For some mRNAs, I agree. But for the Covid mRNA vaccines, how? You claimed they would be of great benefit. Based on what?

As the whole comment already explains, since intracellular localization of RNA during an infection has a very important role in activation of the innate immune response it is obviously possible that anything that alters that localization to improve that activation and make vaccines more effective, specially because (again as already explained) viruses use localization of their RNA for the opposite purpose.

-2 ( +1 / -3 )

The article is giving the impression that all DNA in cell is stored in the nucleus:

RNA takes a copy of the information in DNA from its storehouse in the nucleus to sites in the cell where this information is decoded to create the building blocks – proteins – that make cells what they are.

I just wanted to add some relevant information that I thought was missing from the article, regarding the natural cellular processes.

I don't know why you feel the need to argue with everyone. I wasn't referring to the clinical applications, which BTW I tend to side with Bronco on this. The work discussed in the article does have potential, but I certainly would recommend avoiding any treatment based on RNA until what happened with the current mRNA products is addressed openly and people are held accountable...

-4 ( +3 / -7 )

The team is looking for new zip codes.

Something wrong with the old zip codes?

-6 ( +2 / -8 )

Well, the mitochondria have their own genome, which encode several proteins involved in energy production.

If the purpose is to modify energy production it would have no importance from which genome comes the coding for the proteins, the important part is that the RNA still have to be delivered to the mitochondria to fulfill that role.

Except for the RNA that is made in the mitochondria...

-6 ( +1 / -7 )

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