RNAi

RNAi is an arrestingly interesting little mechanism for protecting the health of cells. The “i” stands for interference, and with good reason. RNAi is made up of a series of molecules which work to detect and destroy possible viruses and RNA which could be viruses.

It was first detected in 1986 when an attempt was made to make a really, really purple flower. The reason was purely for aesthetics, but it would prove to be far more important.

Knowing the gene which coded for purple pigmentation in petunias, geneticists made the logical conclusion and figured adding a bunch of those genes to the flowers would increase the depth of purple coloring in them. But as it turned out, they were wrong. In fact, they were remarkably wrong. Instead of deep purple flowers, they produced white flowers. Not a hint of purple anywhere.

No one had an answer to why would be. It took 12 years until researchers came up with the answer (and another 8 until they were awarded a Nobel Prize).

When viruses invade a cell, they ‘seek’ to make copies of themselves by utilizing the available DNA source. Post-transcription, this comes out with a funny shape due to the RNA making a mirror image of itself. The RNAi then recognizes this strange shape and destroys it with dicers. But it doesn’t stop there. Any sequence which comes out of the nucleus thereafter is also destroyed. This prevents any of the viruses (hopefully) from being translated and replicating (thus exploding out of the cell and infecting other cells).

Something similar happened when the geneticists tried making the super purple flowers. There wasn’t a mirror-image RNA sequence, but there was a funny sort of shape created by all the extra purple pigmentation genes. The RNAi recognized this as a potential virus and began destroying it. All of it. This meant there were no genes for purple getting translated into proteins.

Example petunia plants in which genes for pigmentation are silenced by RNAi. (http://en.wikipedia.org/wiki/Rnai)

Example petunia plants in which genes for pigmentation are silenced by RNAi. (http://en.wikipedia.org/wiki/Rnai)

So far this is pretty exciting stuff. It’s a post-transcriptional defense mechanism against viruses no one ever knew existed. But it has so much more potential than just as a passing curiosity.

Think about it. If RNAi can essentially turn off genes by destroying them through a sort of sequence-detection, then what stops it from curing diseases? This discovery has the serious potential to cure all the major ailments facing the world today: AIDS, cancer, Alzheimer’s. There has already been success in treating macular degeneration. This is a disease where too many blood vessels are growing in the eye. It damages the retina over time and makes vision majorly cloudy and blurry. There are simply too many genes for blood vessels being produced. But one way to stop this disease is to stop that blood vessel growth. To achieve this, a patient is given an injection which contains a copy of the gene with its mirror image (two mirror strands of DNA). The RNAi detects this misshape and destroys it. It then destroys all other likewise sequences. The same principle could be applied to any number of diseases.

There is an excellent NOVA video on RNAi which can be viewed here. It’s certainly worth watching (and only 15 minutes long).

That link

I posted a link earlier. Here it is again.

However, though researchers have been able to show how RNA’s component molecules, called ribonucleotides, could assemble into RNA, their many attempts to synthesize these ribonucleotides have failed. No matter how they combined the ingredients — a sugar, a phosphate, and one of four different nitrogenous molecules, or nucleobases — ribonucleotides just wouldn’t form.

Sutherland’s team took a different approach in what Harvard molecular biologist Jack Szostak called a “synthetic tour de force” in an accompanying commentary in Nature.

“By changing the way we mix the ingredients together, we managed to make ribonucleotides,” said Sutherland. “The chemistry works very effectively from simple precursors, and the conditions required are not distinct from what one might imagine took place on the early Earth.”

Like other would-be nucleotide synthesizers, Sutherland’s team included phosphate in their mix, but rather than adding it to sugars and nucleobases, they started with an array of even simpler molecules that were probably also in Earth’s primordial ooze.

They mixed the molecules in water, heated the solution, then allowed it to evaporate, leaving behind a residue of hybrid, half-sugar, half-nucleobase molecules. To this residue they again added water, heated it, allowed it evaporate, and then irradiated it.

At each stage of the cycle, the resulting molecules were more complex. At the final stage, Sutherland’s team added phosphate. “Remarkably, it transformed into the ribonucleotide!” said Sutherland.

According to Sutherland, these laboratory conditions resembled those of the life-originating “warm little pond” hypothesized by Charles Darwin if the pond “evaporated, got heated, and then it rained and the sun shone.”

I figured I’d have more to add to this, but I don’t. At best I suppose I should point out that this experiment shows that general principles can result in RNA: do such-and-such in a certain order and you’re on your way. That’s an oversimplification, but it makes comprehending the origins of life a bit easier.