Been thinking quite a bit lately about the mechanics of how DNA and RNA interact, and more specifically how RNA is constantly shaping DNA in response to external environment. I’ve been caught up on the idea that every cell in every organism is the result of a sustained chemical reaction stretching back billions of years to the initial catalytic spark(s?) that set all of this in motion.
Individually DNA and RNA have fatal flaws which should prevent this type of sustained reaction, DNA being too cumbersome and metabolically inefficient to translate the environment and RNA being too vulnerable to the external environment to sustain the metabolic chain reaction. But together, they provide an interesting mechanism for allowing adaptation while sustaining the chain.
RNA may be guiding DNA rather than RNA being merely products of DNA. The entire process of meiosis is seems like an RNA bomb going off, mixing environmental influence encoded in gametes or RNA payload local to the gamete.
What if we are still in RNA world, with selection, competition, etc all being artifacts of changes in RNA expression encoded into DNA, rather than DNA providing the expression template for RNA? RNA could be held as the “spark of life” given persistence by DNA.
We can focus on RNA to tell us all we need to know about the organism right now, and perhaps even defining an organism and it’s state by expressed RNA. All of our short term manipulations of organism function are achievable through changes in RNA expression. For longer term changes, those beyond the lifespan of an organism, we can manipulate or create branches in that metabolic chain (and examine past information about RNA response to environment) through DNA.
Under this framework, it gives us an explanation for the expression heterogeneity of many expressed traits, the DNA itself isn’t as important to the individual RIGHT NOW as RNA expression is. We are advancing into a period where many “genetic diseases” are being addressed by inducing changes in RNA expression, and it’s foreseeable that in the not too distant future that we may be able to completely control all aspects of an organism state by manipulating RNA expression directly.
Imagine a sparkler firework, with the RNA being the actual sparkler part of the effect. Environmental conditions over time represent the unburned part of the sparkler, and DNA being the burned part of the sparkler. DNA is a product of the chemical reaction of life, a reaction that gets transferred from sparkler to sparkler as long as environment allows.
Edit: My brain keeps wanting to frame this under the “mind/body” construct, with RNA being the literal mechanical representation of “mind”, and DNA representing “body”.
Think of DNA as a record of what was and RNA as a record of what is. What was may influence what is, but what is reciprocally modifies the record of what was. A genetic disease like Huntington’s may influence what is (or current state), however with changes to RNA expression Huntington’s will not express (or will only express with the right combination of RNA expression).
Edit 2: Heh, another metaphor of environmental/RNA effect might be that of a wind which pushes behavior/cellular outcome in a particular direction. Strength of the wind, collection of individual wind sources, duration of wind, etc, all combine to influence the outcome of both the individual cell at the moment of “conception” to the fate of every single cell and the resultant collective behavior of them.
Because these winds are variable, pervasive, and the sources many, the overall effect of them is hard to really grasp, but it is the effect of RNA expression which determines whether or not a benign cell becomes a cancerous one, or whether an astrocyte signals a microglial pruning session for specific information. These “winds” from both inside and out are ultimately what shape the behavior of the individual, while the individual itself is a “wind” that reciprocally effects the biological reaction that is “life”.
As with all things weather, it’s impossible to know why one set of high/low system shear results in devastating tornados while another may result in a perfect day to fly a kite because we don’t really have a grasp on system complexity yet. We can infer hints and make probability calculations, for example some systems are more likely to develop a particular way than others, but the system is constantly churning and reacting to each other in a never ending (we hope) swirl of entropy.
The butterfly effect metaphor is fairly apt here, every small effect contributes to larger effects elsewhere. Some butterflies get caught in the hurricanes of their own creation, small storms localized around them and disrupting everything around them. Getting into smooth air takes an awareness of the invisible patterns around them, and not all are strong enough to survive their own (or other individuals) storms. In another individual, they are strong enough to not just survive their hurricane, but learn to control their storm and direct it. These can create storms or smooth air, but still have to abide the entropy of the system as a whole.
By investigating real time RNA effects longitudinally, we may finally be on the path to understanding and manipulating the wind.
Just realized this presents a potential problem for a lot of RNAseq work being done.
In vitro oogenesis from murine premeiotic germ cells using a new three-dimensional culture system – The “spark of life” at “conception” has been a long standing mystery to me, why we can’t replicate it consistently (and all that says about biogenesis) or why it even appears to be required. And here the first step in turning the metabolic crank on the way to meiosis is explored, that RNA form a continuous bridge between the “current/child” and “former/parent” branches of the biological reaction. They’ve discovered the shape of the “metabolic key” consistent with their experimental conditions, a metabolic key with fingerprints going back billions of years.
ISOLATION OF TOTAL RNA FROM POLLENS – Eukaryotes are “born” of the same chemical reaction, and even “life” which appears significantly mechanically “different” from ours still require a passed on metabolic key to “unlock” a new branch on the chain.
Hypoxia induces alterations in tRNA modifications involved in translational control – How does a freediver literally change the mechanics of their body to accommodate the behavior? How does a sprinter go faster, or “thinker” think more deeply? RNA allows organisms to adapt to their environment in a deliberate way, vs. the purely chance mutation/environmental pairing in the form of DNA.
Paternal methotrexate exposure affects sperm small RNA content and causes craniofacial defects in the offspring – The oocyte isn’t all that’s transferred during reproduction, animal/plant sperm is loaded is environmental data encoded by RNA. The expression of DNA is entirely dependent on the RNA load both inside and outside of the individual cell. We can modify not just “internal” traits”, but “external” ones as well. I’m probably starting to sound like a neo-Lemarckist now.
Sperm RNA code programmes the metabolic health of offspring – Opinion piece, but the depth and width of information transfer through RNA is really weakly explored at this point. We can be relatively sure though that core metabolic function of offspring are affected by RNA load, sometimes significantly so.
One of the most considerable divergences I have with psychiatry is whether or not “depression” is a “disease”. I’m strongly in the “normal function”/reaction to environment camp, however a significant thorn for me is work which demonstrates pretty consistent susceptibility along genetic lines. Worse for me, is that genetic susceptibility seems to be almost completely random and occasionally just blinks out of existence altogether. This is especially true for “autism” related work. Then we get into the “Asperger’s” gender imbalance issues with the same.
With this particular piece of work it becomes more apparent how changes in RNA expression can modify the construction of offspring in a really profound way. How certain programming can leave an individual pre-disposed/vulnerable to “depression” due to programming changes during development, even with the same genes as others. It explains why “Apserger’s” is male loaded and arbitrary (heavily environmental), compared to other phenotypes which may be encoded in DNA itself.
Small RNA perspective of physical exercise-related improvement of male reproductive dysfunction due to obesity – I think this might be more hyperlipidosis than exercise itself.
Sperm RNA-mediated epigenetic inheritance in mammals: challenges and opportunities – It makes me wonder how complex the informational load passed is, what is the contour of something like intergenerational trauma? It also underlines how terrible most animal models for human research, are we even paying attention to what information is being transferred when the models are being bred?
Epitranscriptomics in metabolic disease – “Moreover, the epitranscriptome in the parental generation can affect organismal phenotypes in the next generation.” DNA is not the only information being passed.
Transgenerational transmission of reproductive and metabolic dysfunction in the male progeny of polycystic ovary syndrome – PCOS as an environmental effect? Maybe.
A paternal protein facilitates sperm RNA delivery to regulate zygotic development – Should not that information transfer doesn’t require male/female mechanics and there are quite a lot of examples of the process without it, but it does require a “control” and “environment sensitive” component.
Examining parent-of-origin effects on transcription and RNA methylation in mediating aggressive behavior in honey bees (Apis mellifera) – Change the expression, change the behavior.
RNAenrich: a web server for non-coding RNA enrichment – Something to waste time on… http://idrblab.cn/rnaenrich/