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I am a mechatronics engineer who stopped learning biology after high school - but this is bothering me.

mRNA is, if I recall correctly, created in the nucleus of the cells and migrates out of the nucleus inside the cytoplasm where it will be translated by ribosomes.

mRNA vaccines inject mRNA molecules inside the body, which are apparently transported by their nanolipidic particle coating across the cell membrane, correct?

I understand that the DNA→mRNA transcription is probably not reversible, but I do not understand how the mRNA is only able to cross the nucleus-cytoplasm membrane in one direction.

Care to explain? Bonus kudos for clarifications on the rest of my doubts.

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    $\begingroup$ mRNA vaccines are not "transported" by their lipid coating (no active transport involved). It's just that lipids are attracted to the nonpolar plasma membrane and expelled from polar water. $\endgroup$ Jan 3, 2022 at 16:21

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Nuclear pores control what gets in and out of the nucleus. In general, mRNAs are only allowed out, they don't go back in. Reverse transcriptases, of course, will put mRNA back into DNA, but only some viruses, like HIV, have those enzymes.

https://portlandpress.com/biochemj/article-abstract/477/1/23/221793/Into-the-basket-and-beyond-the-journey-of-mRNA?redirectedFrom=fulltext

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  • $\begingroup$ Interesting, thanks! Do you mean that, unless a person is infected by rare specific viruses, no reverse transcriptase is present in the body and therefore the mRNA cannot reenter the nucleus? $\endgroup$ Aug 19, 2021 at 18:02
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    $\begingroup$ It is very hard to categorically say something is impossible in biology; there are always exceptions. But your cells are full of your mRNA all the time. When you get infected with most viruses, like COVID, there is foreign mRNA in your cells. In general, this does not cause permanent change to your DNA, let alone clinically pathogenic change. $\endgroup$
    – swbarnes2
    Aug 19, 2021 at 23:22
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    $\begingroup$ Just note that reverse transcriptase works in the cytoplasm to create a DNA copy of an RNA, so it does not allow mRNA transport to the nucleus, it just creates DNA which could then be transported to the nucleus. $\endgroup$
    – Armand
    Aug 19, 2021 at 23:58
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    $\begingroup$ I think this is the beginning of a good answer, but it doesn't directly address OP's question: "but I do not understand how the mRNA is only able to cross the nucleus-cytoplasm membrane in one direction". Yes, nuclear pores control the flow of mRNA out of the nucleus, but they also allow things into the nucleus (like proteins). What is the mechanism by which mRNAs are exported but not imported? $\endgroup$
    – acvill
    Aug 20, 2021 at 16:38
  • $\begingroup$ @acvill: this would indeed be particularly interesting to know! $\endgroup$ Jan 5, 2022 at 16:54
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Transcription Regulatory proteins are able to enter into nucleus because they posses a specific strings of amino acid sequence called Nuclear Localization Sequence. Nuclear Pore Complex don’t let anything without that sequence pass. Nucleus membranes are temporarily dissolved during cell division and reconstituted once the process is complete so technically it’s a possibility that some enzymes could happen to be there. However during cell division, DNA is all wrapped up (DNA-nucleosome-chromatin-chromosome) so not much regulation (much less damaging alterations) can be done during this time. And let’s just say things do go wrong and this particular cell starts to act wonky, your immune cells will recognize the “defective” cell and either engulf it to destroy it or trigger its self destruction through Apoptosis. Pretty neat huh? Inspite of all the failsafe mechanisms, some viruses do manage to disrupt DNA by inserting transposons which in some incidences could trigger/suppress oncogenes, protooncogenes, tumour suppressor genes etc with dire consequences.

Sorry David! Pardon my zeal for proteins. My comment was more for the previous posters and not the OP. Post transcription, mRNA is modified (introns removed, spliced), 5’capped, Poly A tailed added on. 7-MethylGuanosine m7G cap plays an important role in mRNA transport and metabolism. m7G Cap attracts and binds proteins such as eukaryotic translation initiation factors and Cap Binding Proteins. They not only guide mRNA where to go (ribosomes on ER) but also protect them from being degraded by exonucleases (very efficient enzymes that break down RNA and DNA) mRNA has a lifespan of mere 1-3minutes. So to answer your question, cytoplasmic mRNA (foreign or m7G capped cellular RNA) tend not to make it back because

  1. The proteins it’s bound to lack the Nuclear Localization Sequence to get past the Nuclear Pore Complex or 2. Gets degraded very quickly by exonucleases.

Reverse Transcriptase (RNA dependent DNA Polymerase) is not just found in viruses. Telomerase (that lengthen telomer caps on chromosomes) also is a reverse transcriptase. Look up human TERT. Like all polymerases it needs specific binding sites and requirements. RT just doesn’t transcribe any ol RNA into cDNA hybrid FYI. The viruses that insert viral genome into cellular DNA have evolved to bypass all the cellular fail safes.

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  • $\begingroup$ Welcome to SE Biology. Please finish the Tour. Please also read the question and note that it is about the transport of mRNA. Your answer is about proteins and makes no mention whatsoever of mRNA. $\endgroup$
    – David
    Dec 1, 2023 at 22:23
  • $\begingroup$ Sorry I can’t spend any more time specifically to look up citation to back up my post. randomly came across it and sensed an underlying concern regarding mRNA vaccine becoming incorporated into your DNA. For reasons outlined above the chances are extremely slim to zilch. Don’t get me started on the amount of noncoding and considered junk DNA already on our chromosomes. As for citations, you can easily look it up based on the names I provided or I’m sure other cell biologists can back me up. Should be working or spending time with my kids anyway. Adios and hope I helped OP $\endgroup$ Dec 2, 2023 at 4:45
  • $\begingroup$ @NunyaBeezenez Welcome to Stack Exchange! This site works different than most others. Answer posts are absolutely expected to support their assertions by citing references and including links. $\endgroup$
    – uhoh
    Dec 2, 2023 at 9:55

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