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Why does the addition of a 5' cap and that of a 3' tail involve guanine and adenine respectively? Why aren't any of the other two bases added to an mRNA to protect its ends or act as a signal to transport it to the cytoplasm?

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    $\begingroup$ Although I can see why you posed your question in the way you did, it is actually two separate questions. The problem with this is you have received an answer that I regard as a reasonable speculation about the polyadenylation, but not about capping. And as @KaPy3141 makes clear, you should realize that answers to questions of this sort are most often only opinions, and the answer may well be “we don’t know” or “perhaps just chance”. $\endgroup$
    – David
    Jul 31 '20 at 17:03
  • $\begingroup$ Yeah, I understood that after reading the answer @KayPy3141 wrote. And, I could make sense of the speculation about polyadenylation alone, not about capping. I was just wondering if there was any explanation to each of the processes. As you said, turns out it may be just chance. $\endgroup$ Aug 1 '20 at 18:40
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    $\begingroup$ I usually try to alert students to all the possibilities of this sort of thing: chance, some structural feature of the molecule that makes it “better”, or its easier to make because the precursors or enzymes are already there or it involves fewer synthetic steps than alternatives. There’s a common tendency to assume it must do the job better, and answers of that sort tend to get accepted uncritically. $\endgroup$
    – David
    Aug 1 '20 at 18:53
  • $\begingroup$ As others have pointed out, any answer to this is speculative, there is no reason why it would be impossible to use some other bases. It might be helpful to point out that there ARE alternative 5' caps that are occasionally used in living cells, based on coenzyme A, NAD, FAD, and others, see for example: pubmed.ncbi.nlm.nih.gov/27383794 $\endgroup$
    – biohacker
    Aug 2 '20 at 19:43
  • $\begingroup$ As David correctly pointed out, my listed theoretical 'reasons' are purely speculative and come closer to a collection of facts that seem interesting for someone who asks the OPs question. In this context it's hard to not fall in the category of the "chicken-egg problem". In the end, all reasons are pseudo-reasons describing phenomena by other phenomena that cannot be explained and will lead to "because it is like that" after some iterations of "why?". $\endgroup$
    – KaPy3141
    Aug 3 '20 at 9:40
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I don't think definite answers exist but I can think of theoretical reasons:

  • First, Poly A tail can efficiently be synthesized because ATP is the most readily available nTP, being the main energy source.

  • More to the mechanism, but this is no explanation to the evolution: The termination sequence 'TTTATT' on the DNA template and 'AAUAAA'on the RNA is the start of poly-adenylation. But this falls in the 'chicken-egg problem' category.

  • As a bioinformatician, I happen to know, that 3'UTR is highest in A-content of the 3 genomic contexts and the 5'UTR is highest in G-content of the 3 contexts, so possibly these post-transcriptional modifications further strengthen the compositional differences of the contexts.

  • For the poly-A tail it might also be relevant to mention that G or C sequences have higher propensities towards structure due to amount of hydrogen-bonds.

I hope there were some helpful pieces of information.

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