lncRNA are very weird and I think they challenge some of the common, traditional assumptions about how cells work. Basically, the traditional view of RNA was that it's a messenger between the DNA and proteins. That is, it just functions a way to transfer genomic information to the protein factories (ribosomes). There were some widely known exceptions to this, like ribosomal RNA, which forms essential parts of the structure of ribosomes, so it's not just a messenger, it actually has a functional role in building a key cellular machine. My sense was that was viewed as a weird edge case that ribosome biologists were concerned with.

Anyways, there's been an explosion of different classes of RNA in the past decade or so. This has been driven by new techniques in RNA sequencing technology that allow us to detect and sequence RNA in a more unbiased and high-throughput way. What we saw was a huge number and variety of RNA molecules in cells that don't look like they encode any protein. So, this fundamentally breaks that assumption about RNA's role as "just" a messenger.

The best characterized class of these weird new non-coding RNA's is probably micro-RNA. They're very short stretches of non-protein-coding RNA, and it seems that they bind to other sequences of RNA and prevent their translation to proteins. So, RNA has at least one layer of self-regulation. Then we see long non-coding RNA. They can act as "sponges" or buffers of microRNA by preferentially binding to miRNA, preventing the micro-RNA's interaction with their normal protein coding RNA targets. So, there's another layer: long non-coding RNA buffers microRNA which inhibits translation of messenger RNA. Further the long RNA can also condensate into these structures that are similar to droplets of oil in water. They're transitory structures that form and dissolve then reform quickly and repeatedly. What they do is still a bit vaguely understood but they seem to bring together very weakly interacting proteins and RNA in concentrations that wouldn't be possible just by diffusion within the cell. So, there's another layer of regulation: long coding RNAs form condensates to that allow interactions between proteins that wouldn't happen otherwise.

All of this is complicated by the fact that these things have other weird properties. They aren't expressed very frequently, so they're hard to detect. They're not very well conserved evolutionarily, i.e. their sequences diverge rapidly between species. They don't really have fixed structures, they're more just like floppy, sticky noodles. This would typically indicate they're not functional or at least non-essential. How could this be important? It's an RNA that doesn't make a protein, isn't very abundant, has no defined shape, and evolution doesn't seem to care much about the details of its sequence.

*But*, as this paper shows, they're absolutely essential for cellular function. If you take them out of cells, the cells die.

So, all that to say that the idea of biology as working like a little computer; just a series of linear information transmission steps, is probably rather misleading in many cases. Instead it's a tangled mess of weak interactions that depends on subtle biochemical effects like condensation. It's noisy and imprecise at the molecular level, but all the self-interacting layers of regulation and interaction somehow give rise to remarkably precise and adaptive responses at the tissue and organismal level.