[HN Gopher] RNA repair mechanism discovered in humans
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RNA repair mechanism discovered in humans
Author : wglb
Score : 181 points
Date : 2023-05-13 01:20 UTC (21 hours ago)
(HTM) web link (phys.org)
(TXT) w3m dump (phys.org)
| irrational wrote:
| My grandmother just celebrated her 100th birthday. She still
| lives on her own, drives, does her own cooking, walks unassisted,
| etc. When I mentioned I was going out of town for her 100th
| birthday party, people kept saying she must have good genes.
| Maybe so. Maybe she has some sort of really good RNA repair
| mechanism.
| ggm wrote:
| If she has a good RNA repair mechanism isn't it heritable or do
| you posit she bought it or made it from wool and toothpicks?
| irrational wrote:
| Maybe inherited, maybe a mutation unique to herself.
| svnt wrote:
| Your response seems to miss the difference between the
| terms inherited and heritable (because it could be
| heritable without being inherited), but your point is
| valid: whatever she has may be cognitive, biological, or
| otherwise, and may or may not have heritable aspects.
| samstave wrote:
| [flagged]
| tbirdny wrote:
| I'm looking forward to ways we can increase levels of C12orf29 or
| supplement it somehow in hopes of boosting RNA repair.
| throwaway12245 wrote:
| Human tissues may be fine tuned to need a specific range of
| C12orf29 molecule quantities: too many or too few might be big
| problems. See https://www.proteinatlas.org/search/C12orf29 for
| the gene expression for various tissues.
| p1esk wrote:
| Is this relevant for anti-aging research? How significant is this
| paper in that context?
| spurgu wrote:
| I suggest you look into David Sinclair, he's done some
| interesting research with epigenetics.
| shpongled wrote:
| David Sinclair is considered to be a quack (bordering on a
| fraud) by many within the scientific community.
| vhcr wrote:
| You're gonna need to backup your claim, because a quick
| google search didn't lead me to anything.
| meowkit wrote:
| So I guess we're at the point which Harvard Medical School
| isn't good signal?
|
| https://sinclair.hms.harvard.edu/people/david-sinclair
|
| Who considers him a quack? Why should I believe them?
| stubybubs wrote:
| Larry Ellison, is that you?
| evrimoztamur wrote:
| I believe that humans have not yet created any system more
| complicated than our own bodies. In turn, I think the same claim
| holds for our own brains too.
|
| We are in for a series of revelations that will deeply alter the
| way we understand the microscopic intricacies that hold us
| upright and posting on internet forums.
|
| Exciting things happening in the field!
| motoboi wrote:
| The brain is the most complex object in the known universe.
| layer8 wrote:
| By what measure of complexity, and what definition of
| "object"?
|
| Arguably the totality of all lifeforms on earth, which are
| all physically connected to each other by their common
| genealogical graph (and by Earth as their environment), is
| more complex, because it contains all the brains.
| anonymouskimmer wrote:
| Comparing a brain to anything which encompasses a brain, is
| tautological. In debate ("arguably", as you say), this is
| the equivalent of "infinity plus 1", which is a fallacy. So
| obviously the GP could not have been referencing anything
| which contains a brain as an "object".
| layer8 wrote:
| Which is why I asked about what qualifies as an "object".
| The brain itself is a composite, so why does a larger
| composite not qualify?
| anonymouskimmer wrote:
| A larger composite (which contains a brain) can not
| qualify by the very nature of the proposition put forth.
| At least in adult debate (where "infinity plus 1" is seen
| as fallacious). Larger composites that do not contain a
| brain are fine by me, though I'm not the person you
| originally responded to.
| BobbyJo wrote:
| > A larger composite (which contains a brain) can not
| qualify by the very nature of the proposition put forth
|
| Personally don't see how this follows.
|
| "There is no larger circle than this ball bearing!"
|
| "What about the wheel it's used in?"
|
| "That's tautological!"
| quijoteuniv wrote:
| Known by who?
| lksjdflksdj9 wrote:
| ^^ this
| khazhoux wrote:
| In common parlance, "known universe" refers to the extent
| of the universe that is observable by human beings on the
| planet earth.
|
| Hope that helps!
| throwaway12245 wrote:
| More complex than the immune system?
| Malic wrote:
| Gonna have to agree that at the very least, the immune
| system is way up there! After reading Philipp Dettmer's
| book "Immune" (recommended), I couldn't help but think,
| "Wow, the API and protocols that this thing has..."
| echelon wrote:
| If the rules that govern intelligence are simple (and
| intuition tells me they are), then the immune system is
| certainly a complicated and prickly beast.
|
| https://en.wikipedia.org/wiki/V(D)J_recombination is wild.
|
| My money is on the immune system being more complicated.
| anonymouskimmer wrote:
| I don't want to double post:
| https://news.ycombinator.com/item?id=35933061
| hkt wrote:
| This - the immune system is fiercely complex, and as I
| understand it there's reason to believe we don't yet know
| all the _types of cell_ that are in it. I could be wrong
| about that - I 'm not an immunologist - but seem to recall
| reading such in the last few years.
| anonymouskimmer wrote:
| To address you and the GP.
|
| > More complex than the immune system?
|
| Possibly. From 2016:
| https://www.nature.com/articles/nature17316
|
| text in <> are mine.
|
| > The research group behind the current study previously
| showed11 that NHEJ <non-homologous end-joining, an error-
| prone mechanism of double-strand DNA break (DSB) repair>
| is essential for NSPC <neural stem/progenitor cells>
| differentiation, which implies a role for NHEJ-mediated
| DSB repair during normal brain development. It is
| possible that subpopulations of cells in the brain
| display the same types of rearrangements, and that some
| are positively selected. Similar studies in vivo and in
| other tissues are needed to test this hypothesis.
|
| From 2022:
| https://www.nature.com/articles/s41597-022-01508-x
|
| > We show that genome-wide maps of endogenous DSBs are
| highly correlated between experimental replicates up to
| 10 kilobases (kb) resolution, and that DSBs are non-
| uniformly distributed along the genome, in all three cell
| differentiation stages analyzed.
|
| ...
|
| > Our datasets and analytical tools represent a valuable
| resource for exploring genome fragility during human
| neurogenesis and investigating how this might contribute
| to the pathogenesis of NDDs. <neurodevelopmental
| disorders>
| BulgarianIdiot wrote:
| Complexity is a bit subjective. Society is ostensibly more
| complex than us, because it includes us. Of course, so far
| society is more often less than the sum of our parts, than the
| other way around. Growth is hard.
| rowanG077 wrote:
| I disagree with that. A whole can be less complex then its
| constituent parts. This is the entire point of abstraction,
| you can hide irrelevant complexity.
| themodelplumber wrote:
| Which is different from saying a whole can't be more
| complex than its parts...
|
| Also, abstraction is an activity which often serves to make
| additional room for new emergent complexities.
| BulgarianIdiot wrote:
| Abstraction is a way to break down a system to fit in our
| minds & simulations, including for the purpose of designing
| it, but it's not what a system truly is, and it's not how
| it behaves. It's a compromise, like for example your
| calculator has 8 digits, and shows E if you need more, but
| this doesn't mean math in the universe is limited to 8
| digits.
|
| You can't just decide the fact society is made of humans is
| an irrelevant detail and model them with little rational
| balls, or whatever you came up with. Because the balls
| wouldn't do what we do. And I completely disagree it
| doesn't matter what the human body does. The human body
| matters to society a great deal, actually. Say, pollution
| in cities is absorbed by your human body, and affects
| health, even mental health, and how long you live. This
| affects social dynamics immensely or doesn't it? We've had
| entire social movements based on our understanding of the
| human body, how we categorize in various ways the human
| body, and violence done against the human body, choices
| about the human body, how we treat it medically and so on
| and so on. Countless examples.
|
| Of course you can successfully model specific narrow
| events, do a representative sample and try to approximately
| guess, say the outcome of elections. Doesn't always work,
| but in this very simple example, you can abstract things.
| But you need to still abstract with deep understanding of
| what is abstractable for that specific point in space and
| time.
|
| This approach fails miserably if you need to predict how
| society will evolve over time, and more fine-grained
| detail. Say, just 2 years ago society was largely ignorant
| of the AI revolution bubbling up based on work by Google &
| subsequently OpenAI. This is something society did,
| irreducibly, based on the people in it, and their bodies
| and neurons. And no basic statistics model that abstract us
| away would have predicted this.
| postalrat wrote:
| A single cell is more advanced technology that anything we've
| developed so far.
| americanZero wrote:
| [dead]
| qudat wrote:
| Biological systems are unnecessarily complex systems. This why
| the key to understanding ourselves won't happen by studying
| biology, rather by creating AGI.
|
| https://bower.sh/in-love-with-a-ghost
| lifeplusplus wrote:
| i dont a human can create a system this complicated... i dont
| think we can even map it out. if it's done, it'd be done by AI
| and it'd be a black box. we couldn't create an autonomous car,
| we need ai to come up with million rules and parameters. same
| story here just order of magnitudes more complex.
| visarga wrote:
| Can't do it intentionally, but evolution can do it
| unintentionally.
|
| Nature solved this problem of radical open-ended exploration
| through evolution. It takes a lot of time but in a single run
| evolution created all species and life on earth. Evolutionary
| methods also created AlphaGo, AlphaTensor and AlphaFold -
| three AIs that surpass all humans put together in specific
| fields.
|
| Basically learning from massive search and problem solving
| outcomes - that's how you solve hard problems. And if you
| think about it, that's how science works too - so many
| papers, many contradicting each other or trying completely
| different approaches adds up to evolution in the space of
| scientific ideas. Any one human alone can't do it, but all of
| us over a long enough time can do so much more, diversity and
| open-endedness are key.
| DoreenMichele wrote:
| Either the article leaves out something or the title is
| misleading. It's an antioxidant defense system that protects
| against cellular distress.
|
| The article doesn't seem to describe repair work. Did I miss some
| detail?
| jjtheblunt wrote:
| Isn't the repair work that of the RNA ligases, whose particular
| versions for humans are first mentioned here?
|
| > "In order to fulfill their diverse functions in the cell,
| RNAs often need to be chemically modified after their creation
| or repaired after damage," explains Andreas Marx, professor of
| organic and cellular chemistry at the University of Konstanz.
|
| > One chemical reaction that plays a role here is the three-
| step linking (ligation) of two RNA strands at their respective
| opposite ends. This reaction is triggered by specialized
| enzymes called RNA ligases and is present in all forms of life,
| from viruses to fungi and plants. In vertebrates, including
| humans, such RNA ligases had yet to be identified.
|
| > An interdisciplinary research team from Konstanz has now
| discovered the first human RNA ligase of this type, the protein
| C12orf29."
| DoreenMichele wrote:
| Ah. Ok. I see why you would infer that.
|
| But it's an inference -- an assumption that human ligases
| will do what ligases do in other species and that's not what
| the actual research shows, at least not that the article
| indicates.
|
| We've just discovered these. They are investigating what they
| do. Their investigation shows they protect against oxidative
| stress, which is significant.
| dekhn wrote:
| I generally agree with your assessment.
|
| I skimmed the paper and there really isn't any direct
| evidence that it's a "repair mechanism" beyond the apparent
| effects of knocking out the gene: cells die faster, and
| degradation of ribosomal RNA is faster.
|
| The presumed mechanism here would be oxidative
| stress->damage to rRNA->reduced protein
| production/increased error rate in proteins->cell is not
| happy, with the RNA ligase playing the role of repairing
| localized damage caused by stress thus allowing the cell to
| continue at its normal rate.
|
| There also isn't any strong evidence that this system
| resembles the ones seen in viruses and bacteria. There are
| many RNA ligases that have many different roles and the
| variations aren't shared between all kingdoms of life.
| firstlink wrote:
| How does this fit into the
| https://en.m.wikipedia.org/wiki/Central_dogma_of_molecular_b...
| according to which RNA is short-lived?
| getoffmycase wrote:
| RNA is generally short lived. But specific kinds of RNA can
| have longer lifetimes. It's accurate to say that RNA lifetime
| is extremely tightly regulated, and most of the time that means
| that it is short lived. Its lifetime is also extremely short
| compared to DNA and a high percentage of proteins.
| dekhn wrote:
| The central dogma doesn't really cover the form of RNA that is
| speculated to be repaired here: ribosomal RNA.
|
| The central dogma concerns mainly the transcription of DNA to
| mRNA, the reverse transcription of RNA back to DNA, and the
| translation of mRNA to protein. But over time RNA has turned up
| in a wide range of other activities. In this case, ribosomal
| RNA is the functional heart of the ribosome- the machine that
| translates mRNA to protein.
|
| Ribosomal RNA represents a very significant investment of
| resources for the cell and so if it gets damaged, the cell
| won't be able to make proteins as quickly, or the proteins that
| get made might have errors, both of which have dire effects on
| the cell.
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