So it came as rather a shock when, in several 2012 papers in Nature, he and the rest of the ENCODE team reported that at one time or another, at least 75 percent of the genome gets transcribed into RNAs. The ENCODE work, using techniques that could map RNA activity happening along genome sections, had begun in 2003 and came up with preliminary results in 2007. But not until five years later did the extent of all this transcription become clear. If only 1 to 2 percent of this RNA was encoding proteins, what was the rest for? Some of it, scientists knew, carried out crucial tasks such as turning genes on or off; a lot of the other functions had yet to be pinned down. Still, no one had imagined that three quarters of our DNA turns into RNA, let alone that so much of it could do anything useful.
tl;dr - We injected the world with mRNA, hacking at biology, using incomplete knowledge that was not only misunderstood - it may have been outright WRONG.
Dozens of other research groups, scoping out activity along the human genome, also have found that much of our DNA is churning out “noncoding” RNA. It doesn’t encode proteins, as mRNA does, but engages with other molecules to conduct some biochemical task.
Non-coding RNA is not mRNA. It's completely different.
Structurally they're the same building blocks, the difference in definitions is by outcome not structure. It's just what other structures they are keyed to interact with by the specifics of their sequence.
When it comes to hastily man-made analogues with dubious stability and an indeterminable number of unintended byproduct and partially broken sequences mixed in, having some unintended interactions similar to non-coding RNA is eminently possible.
The structures of mRNA and non-coding RNAs are different. Way different. In biology, structure is function.
They use the same nucleotide building blocks, yes (Uracil, Adenine, Cytosine, and Guanine) but even those building blocks are used differently. For example, with microRNA this nucleotide sequence needs to be very specific for it to fold and become double-stranded and form a hairpin loop so it can be recognized by the necessary protein complex, attach, and allow the microRNA to guide it to its target. mRNA does not have such sequences. And the specific nucleotide sequence requires several nucleotides in a row, so a spontaneous mutation wouldn't wouldn't be enough to induce the formation of one.
Why other structures are keyed to interact with RNAs also depends on the modifications an RNA has, rather than its sequence. mRNA needs to have a special methylated guanosine attached to the front as well as a chain of adenines known as the poly-A tail to the end. They both keep the mRNA stable and are recognition sites for the mRNA to be properly used. If the mRNA becomes unstable and breaks apart, it gets targeted for degradation because pieces will now no longer have these protective caps.
rRNA, also known as ribosomes, are so structurally different from mRNA it would be impossible for one to turn into the other spontaneously. Same with lncRNA. tRNA is also capped with specific tags on its ends that are completely different from mRNA, in addition to having essential tertiary structure. And to get these tags occurs during the synthesizing of the specific type of RNA, so you can't just have some random RNA floating by get the wrong tags.
Basically, non-coding RNAs have significantly different structures and these structures are obtained by very specific sequences that mRNA just doesn't have. This doesn't rule out mRNA doing other things - like there is some evidence mRNA-based jabs can undergo reverse transcription - but mRNA to non-coding RNA, nah.
mRNA, even highly unstable mRNA, behaving like non-coding RNA, is not eminently possible. I even tried to check for any evidence of this occurring, nada. It's so improbable it's like talking about alchemy. It's like throwing a bunch of car parts into a tornado and having a road-certified car spat out.
You're misunderstanding the core concept here. I'm not saying mRNA spontaneously becomes healthy, fully-functional non-coding RNA units. I'm saying if you force a huge number of random RNA sequences in there some of them might be just the right structure to foul the functions non-coding RNA normally perform.
It's not throwing a bunch of car parts into a tornado and getting a fully functional car. It's throwing a bunch of random screws and metal shapes into an automated production line and having the production line grind to a halt or even start producing defective units.
For example, randomly cleave the poly A end off an mRNA, and over-methylate the guanosine (enzymatically not easy to do by accident, but chemically it is, such as when you're trying to form a nanolipid delivery capsule under conditions completely atypical for normal biological systems.) and you could have something that looks enough like snRNA that it could potentially mess with transcription or transcription regulation in unforeseen ways.
tl;dr - We injected the world with mRNA, hacking at biology, using incomplete knowledge that was not only misunderstood - it may have been outright WRONG.
They're not talking about mRNA here.
Non-coding RNA is not mRNA. It's completely different.
Structurally they're the same building blocks, the difference in definitions is by outcome not structure. It's just what other structures they are keyed to interact with by the specifics of their sequence.
When it comes to hastily man-made analogues with dubious stability and an indeterminable number of unintended byproduct and partially broken sequences mixed in, having some unintended interactions similar to non-coding RNA is eminently possible.
The structures of mRNA and non-coding RNAs are different. Way different. In biology, structure is function.
They use the same nucleotide building blocks, yes (Uracil, Adenine, Cytosine, and Guanine) but even those building blocks are used differently. For example, with microRNA this nucleotide sequence needs to be very specific for it to fold and become double-stranded and form a hairpin loop so it can be recognized by the necessary protein complex, attach, and allow the microRNA to guide it to its target. mRNA does not have such sequences. And the specific nucleotide sequence requires several nucleotides in a row, so a spontaneous mutation wouldn't wouldn't be enough to induce the formation of one.
Why other structures are keyed to interact with RNAs also depends on the modifications an RNA has, rather than its sequence. mRNA needs to have a special methylated guanosine attached to the front as well as a chain of adenines known as the poly-A tail to the end. They both keep the mRNA stable and are recognition sites for the mRNA to be properly used. If the mRNA becomes unstable and breaks apart, it gets targeted for degradation because pieces will now no longer have these protective caps.
rRNA, also known as ribosomes, are so structurally different from mRNA it would be impossible for one to turn into the other spontaneously. Same with lncRNA. tRNA is also capped with specific tags on its ends that are completely different from mRNA, in addition to having essential tertiary structure. And to get these tags occurs during the synthesizing of the specific type of RNA, so you can't just have some random RNA floating by get the wrong tags.
Basically, non-coding RNAs have significantly different structures and these structures are obtained by very specific sequences that mRNA just doesn't have. This doesn't rule out mRNA doing other things - like there is some evidence mRNA-based jabs can undergo reverse transcription - but mRNA to non-coding RNA, nah.
mRNA, even highly unstable mRNA, behaving like non-coding RNA, is not eminently possible. I even tried to check for any evidence of this occurring, nada. It's so improbable it's like talking about alchemy. It's like throwing a bunch of car parts into a tornado and having a road-certified car spat out.
You're misunderstanding the core concept here. I'm not saying mRNA spontaneously becomes healthy, fully-functional non-coding RNA units. I'm saying if you force a huge number of random RNA sequences in there some of them might be just the right structure to foul the functions non-coding RNA normally perform.
It's not throwing a bunch of car parts into a tornado and getting a fully functional car. It's throwing a bunch of random screws and metal shapes into an automated production line and having the production line grind to a halt or even start producing defective units.
For example, randomly cleave the poly A end off an mRNA, and over-methylate the guanosine (enzymatically not easy to do by accident, but chemically it is, such as when you're trying to form a nanolipid delivery capsule under conditions completely atypical for normal biological systems.) and you could have something that looks enough like snRNA that it could potentially mess with transcription or transcription regulation in unforeseen ways.