EP 23 · 55:23

The “vault” concept: protecting RNA inside protein shells

From JWST's "Little Red Dots," TimeVaults, and the Dawn of Math

Episode
13/21
JWST's Little Red Dots and the early black-hole puzzle, Harvard/Broad's TimeVaults for time-series gene expression, Halaf pottery that may encode geometric sequences—and a quick Cloud9 dark-halo follow-up.
Transcript

719 words · auto-generated from the episode video

55:23extend the recording window? Well, one naive way to do it is just be like delete all the exoomes, all the trash collectors. That's a really bad idea. >> Okay, [laughter] imagine a city without trash collectors. >> Yeah, we don't want that. >> We don't want that. We don't want that. >> Some people say that's what LA is today. [laughter] I will have you know we still have trash and recycling. >> It's not that bad. It's not that bad. But you can imagine that's that's a really bad way of doing things. You can't stop degradation because that stuff is essential for life to keep moving around. So instead, >> what if we could spatially segregate the mRNA and keep it away from the trash collectors? >> Okay. >> Right. We could put it in a vault. Uh-huh. I see. Although although the name vault is actually not for like you

56:05know a vault to store stuff, it actually comes from this 1986 paper by Kerodasha and Rome um at UCLA in the journal of cell biology. This was 1986. Okay. What they were doing was studying coded vesicles which are like just transport spheres that like package a bunch of stuff and then and then move it around the cell. And they kept coming up with this contaminant. Okay. There was a contaminant in their sample all the time. And when they looked really closely at this contaminant, there were these large barrel-shaped organels. >> Okay. >> Okay. And when you went into a electron microscope and took a look at them, these organels resembled vaulted ceilings of Gothic cathedrals. So they

56:47named them vaults. And these things are massive. Okay? They if you look at the scale bar there, that's 100 nanometers. That's like the size of some cells. And these organels are that big, right? And they're the largest nonviral >> ribboucleic protein complex. >> They've got a mass of approximately 13 megains, which is three times the size of a ribosome. The ribosome is the factory that makes proteins out of mRNA. And they're pretty big for just like for for just like single units of stuff, right? Not not really single units. There's like subunits that form together to create a ribosome. But at the end of the day, it's not a fullyfledged organel

57:28with like a membrane and like a a full like, you know, inside and outside. >> This thing 13 megodulins at the dimensions of tens of nanometers and there's a bunch of them in our cells. 10,000 to 100,000 per cell. >> Jesus. >> Okay. A lot of our immune system cells have overexpression of this stuff. >> Okay. >> And what's weird is we still don't really know what they're there for. And they're not essential because if you knock them out in mice, like you just get rid of the protein that makes these vaults, the mice are fine. >> So there's some, you know, there's a variety of things. It's either, you know, evolutionarily over time, we've, you know, no longer

58:10need these things, but they're still around. Yeah. >> Or there's some functionality that we just haven't figured out. We don't really quite know yet. >> And it's it's more likely the latter because there's a lot of stuff that, >> you know, our DNA is made up of introns and exxons. So there's stuff that the DNA keeps inside the nucleus and then there's stuff that gets expressed. This stuff is getting expressed, right? If you have 10,000 to 100,000 per cell, clearly like >> evolution by now should have figured out if if there's no use for this, why waste time and energy like making this stuff, but it's it's being expressed. So there is some reason. We just haven't quite figured out what that is. But the advantage is because it's not critical for function, you can use it as this kind of ideal robust non-toxic chassis

58:53for stuff. >> Okay, so let's get into this vault protein. What does it look like? There's there's a single protein that makes it up that's called a major vault protein. You get 78 copies of this protein and it self assembles. It doesn't need like something to come in and assemble it.

From the episode
  1. EP 23

    JWST's "Little Red Dots," TimeVaults, and the Dawn of Math

    Little Red Dots, TimeVaults biology, and ancient math in Halaf pottery.

    JWST's Little Red Dots and the early black-hole puzzle, Harvard/Broad's TimeVaults for time-series gene expression, Halaf pottery that may encode geometric sequences—and a quick Cloud9 dark-halo follow-up.