I skimmed the paper, and it's interesting that this seems like these were identified purely from scanning public RNA sequencing datasets and then finding things that look like they would make circles. As someone with only a rudimentary understanding of biology and bioinformatics, I'm wondering:
* Has anyone experimentally demonstrated that these RNA sequences actually form circles?
* Is it possible that these are the result of some reaction in the transcription process? (My understanding of RNA transcription is that we sequentially dump some enzymes into a petri dish, so it seems plausible that we could generate novel DNA/RNA not present in the source.)
* Is it possible these are actually ubiquitous, exist in every cell, but we don't have any reliable way to detect them?
>Is it possible that these are the result of some reaction in the transcription process? (My understanding of RNA transcription is that we sequentially dump some enzymes into a petri dish, so it seems plausible that we could generate novel DNA/RNA not present in the source.)
Even if this was plausible, it wouldn't be there at a high enough copy level when using a DNA-dependent RNA polymerase. Let's say the RNA polymerase goes haywire and creates a random string of RNA. Well, you'd just get one exact copy of that string, it'd be unable to use it as a template to duplicate the string, since it requires a DNA template, not an RNA one. A single copy wouldn't be detectable above the noise, and so wouldn't show up in any datasets. (or would be discarded if it did, as noise).
>Is it possible these are actually ubiquitous, exist in every cell, but we don't have any reliable way to detect them?
There is so much more to the RNA world, especially the RNA virus world, than we realize, because RNA is so hard to work with. Humans secrete enzymes that degrade, and those enzymes are extremely durable and wind up everywhere. Also, RNA is generally not good for DNA processing, so lots of DNA prep kits degrade the RNA intentionally. So the overwhelming majority of nucleic acid work is done with just DNA, and RNA viruses are a huge blind spot. That's not to say no one is doing RNA work, just far fewer.
* Has anyone experimentally demonstrated that these RNA sequences actually form circles?
* Is it possible that these are the result of some reaction in the transcription process? (My understanding of RNA transcription is that we sequentially dump some enzymes into a petri dish, so it seems plausible that we could generate novel DNA/RNA not present in the source.)
* Is it possible these are actually ubiquitous, exist in every cell, but we don't have any reliable way to detect them?