14 May, 2009

Nature review: Origin of 'RNA world'

OK this is cool. Really cool. But I suck at chemistry so I'm gonna keep it real simple...

It's a given that life somehow emerged at least once on this planet about 4-4.5 billion years ago. Understanding how this amazing event happened is a major challenge though. There are a multitude of theories out there but problems tend to arise in trying to reproduce the origin of life event in the lab. One theory is that prior to DNA and protein-based life there was an exclusively RNA-based world. Indeed, this theory is probably widely accepted as the most plausible, if not the only possible, scenario.

As I said, each theory has it's own problems, and the RNA-world theory is no different. The main difficulty is how to combine the three elements of an RNA molecule, i.e. the nucleobase, the ribose and the phosphate. In particular, attempts to join together the nucleobase and the ribose have always been met with failure, casting doubt on the likelihood of these molecules spontaneously combining in Earth's early atmosphere...

That is until now.

Researchers Powner et al (1) have published results in Nature showing that a nucleobase and a ribose can combine in plausible early Earth conditions. They achieved this by using a totally different approach to previous attempts. It had long been assumed that the nucleobase and the ribose must have first formed independently and then joined together in a secondary reaction (See FigA). Instead, Powner and colleagues have now shown that the combined nucleobase-ribose molecule can emerge from a precursor molecule, side-stepping the need for both to first form independently (FigB). Specifically, "activated pyrimidine ribonucleotides can be formed in a short sequence that bypasses free ribose and the nucleobases, and instead proceeds through arabinose amino-oxazoline and anhydronucleoside intermediates"

Figure taken from article by Jack Szostak (2)

So this work gives a plausible mechanism for the origin of the 'RNA world'. Pretty cool, isn't it?

Well yes, but I've saved the best part till last.....

The catalyst for this series of reactions that combine a nucleobase and a ribose is........wait for it......


That's right. The third component of RNA is needed for the precursor molecules to form the activated pyrimidine ribonucleotides. Phosphate controls several steps in the reaction. Specifically, it "controls three reactions in the earlier stages by acting as a general acid/base catalyst, a nucleophilic catalyst, a pH buffer and a chemical buffer". Following completion of it's job as a catalyst, phosphate is then incorporated into the molecule at a later stage, thus completing the RNA synthesis. The beauty of this system is incredible, and is described perfectly by Szostak:

Phosphate continues to have several essential roles in the remaining steps of Powner and colleagues' pathway, in one case causing depletion of an undesired by-product, and in another saving a critical intermediate from degradation. The penultimate reaction of the sequence, in which the phosphate is attached to the nucleoside, is another beautiful example of the influence of systems chemistry in this set of interlinked reactions. The phosphorylation is facilitated by the presence of urea; the urea comes from the phosphate-catalysed hydrolysis of a by-product from an earlier reaction in the sequence.

This work represents a major breakthrough in our understanding of how life might have emerged as it has provided an elegant mechanism for the spontaneous generation of RNA. As always, more research needs to be done, but we now have an exciting new perspective on an age-old problem.

(1) Powner et al. Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature 459, 239-242 (14 May 2009)

(2) Jack W. Szostak. Origins of life: Systems chemistry on early Earth. Nature 459, 171-172 (14 May 2009)


Anna Sethe said...

really cool,
but don't waste your time explaining that to Ray et al.
You might suck at chemistry but they can't even spell it.

rhiggs said...

Hi Anna,

Yeah I don't waste any time on that crowd. I try and maintain a fundie-free diet.

Having said that, I do occasionally drop in on Dan's site...

freddies_dead said...

Cool, but ribonucleotides look like ducks so God must still have done it

BeamStalk said...

Very awesome, it shows we are closer to understanding abiogenesis.

Vagon said...

"Cool, but ribonucleotides look like ducks so God must still have done it"

Yeah I mean its not likeit looks like a crocoduck. This disproves round-earthism.

Dov Henis said...


Genomes Are RNAs'-Made Patterns-Manuals

"Repeats protect DNA"

"More On Evolution In The Still RNA World"

Fitting together the pieces of the "still an RNA world" puzzle ?

- Rational probability and possibility that the initial, independent pre-biometabolism direct sunlight-fueled genes (life) were RNAs, who evolved their DNA-images as operational patterns-manuals libraries, and celled and genomed them. They most probably synthesized (and nucleusized) their DNAs manual libraries as their functional organs, to serve as their environmentally stabler than RNA, than themselves, works memory cores.

- Rational possibility that ALL RNAs represent the original archae-genes that since their (life) genesis have been and still are the primary actors, assessors, messengers, operators of all life processes.

- Rational possibility that the RNAs are the environmental feedback communicators to, and modifiers of, the genomes, that the RNAs are the effectors of the desirable biased genes expressions modifications, of enhanced energy constraining for survival.

Dov Henis
(Comments From The 22nd Century)
28Dec09 Implications Of E=Total[m(1 + D)]
Cosmic Evolution Simplified

Dov Henis said...

On RNA Cell Faring Programs

The chicken and egg story...
RNAs are still Earth's primal organisms, who made the genome as their functional working templates...(BTW, they also made the cell enclosing membranes as their functional organs...)

Cell Faring Programs Involve Transcription Factors,
Made By RNA Genes From DNA Templates Made By The Genes,
Transcription Factors That Activate Genes,
The RNA genes.

A. TGF-beta acts as a transcription factor
Transforming growth factor beta (TGF-beta) is a protein synthesized by skeletal cells, found in most species, that controls proliferation, cellular differentiation, and other functions in most cells.

B. Myc produces DNA binding protein
myc = Any of a group of vertebrate oncogenes whose product, a DNA binding protein, is thought to promote the growth of tumor cells. Possibly from my(elo)c(ytomatosis virus).

C. From "How Cells Protect Themselves from Cancer"

- Two protection programs work together, through an interaction with normal immune cells, to prevent tumors.

- The oncogenes themselves can activate these cell protection programs in an early developmental stage of the disease. They trigger apoptosis (programmed cell death), and senescence (biological aging) is triggered by another oncogene, the ras gene. Senescence stops the cell cycle, and the cell no longer divides.

- First Myc oncogene triggers apoptosis in the lymphoma cells. The dying cells attract macrophages of the immune system, which devour and dispose of the dead lymphoma cells. The thus activated macrophages secrete messenger molecules (cytokines), including the cytokine TGF-beta, which can block the growth of cancer cells in the early stage of a tumor disease, by switching on the senescence program.

D. From "Red and white blood cells come from different sources" ???
Researchers (in mice) distinguish two different types of blood stem cells??? All stem cells are not created equal???

- In the blood, millions of diverse cells die every second. To keep up with this loss, stem cells continually divide to create the correct balance of cell types, which include oxygen-carrying red blood cells and a menagerie of immune cells.

- The hitherto thought was that one single type of blood stem cell in the bone marrow continually replenish the blood system throughout a person's life. Recent studies hinted that blood stem cells have distinct behaviors, but the different kinds of cells were pinpointed only now, using different dye stain markers.

- While each type of stem cell was able to produce every kind of blood cell, the team found a clear difference in end-products ratio: One type of stem cell produced many more red blood cells than immune cells, and vice versa.

- What’s more, as the mice aged, the relative amounts of these stem cell types shifted. As mice got older, the stem cells that create more red blood cells made up a larger proportion of all stem cells, beating out the immune-cell–biased stem cells.

- The researchers also observed that TGF-beta1 spurs red blood cell–producing stem cells to divide and at the same time represses division of their immune cell–producing counterparts. They suggest that these different actions of TGF-beta1 may allow fine-tuning of the ratio of different stem cell "subtypes".

Dov Henis
(Comments From The 22nd Century)
03.2010 Updated Life Manifest
Genomes Are RNAs-Made Patterns-Manuals

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