Part 4 (2/2)

Yet despite being made of similar ingredients, DNA and RNA are quite different. This is because DNA uses a different sugar than RNA (deoxyribose versus ribose) to join its alphabet. DNA is rigid and stable, double-stranded, and a.s.sumes a beautiful staircaselike structure. RNA is floppy and unstable, usually single-stranded, and sometimes tangles up into knots. These sister molecules have completely different personalities.

Researchers have known for decades that DNA stores our body plans-genetic information that is pa.s.sed on through generations. They thought that RNA was merely a middleman, helping translate the DNA into proteins that do most of the work in the body. (If DNA is the blueprint, proteins are both contractors and building materials.) But it is time for mighty DNA to move aside. Beginning with the discovery of RNAi, researchers now realize that RNA is at least as important as DNA, if not more so.

Running Interference RNAi is a natural gene-silencing process that has been preserved as a survival tool throughout billions of years of evolution. This gene-silencing effect was described decades ago-after a series of frustrating failed experiments-and today, at long last, its mechanism is known. RNAi brutally hijacks a special form of RNA RNAi brutally hijacks a special form of RNA that is doubled up, cleverly termed double-stranded RNA, and chops it into bits like a serial killer getting rid of a body! that is doubled up, cleverly termed double-stranded RNA, and chops it into bits like a serial killer getting rid of a body!

This is useful to the cell in many ways. For example, double-stranded RNA, otherwise rare, is a common component of many viruses. Virus-infected plants sense the wrongful presence of double-stranded RNA, and set RNAi in motion-recruiting a series of protein machines to interfere with the rogue invader's dastardly plans by slicing up its genes.

Interfere is too gentle a term since RNAi works through a molecular machine, descriptively named is too gentle a term since RNAi works through a molecular machine, descriptively named dicer, dicer, that cleaves double-stranded RNA into much smaller pieces. Those broken fragments are worse than useless to the virus, because they stick to other viral RNAs, gumming up their ability to schedule production time on protein-making ribosome factories. that cleaves double-stranded RNA into much smaller pieces. Those broken fragments are worse than useless to the virus, because they stick to other viral RNAs, gumming up their ability to schedule production time on protein-making ribosome factories.

RNAi dicer dicer destroys viral RNA; no RNA means no new viruses and a healthy plant. destroys viral RNA; no RNA means no new viruses and a healthy plant.

Today, researchers have unearthed RNAi in virtually every organism, from plants to pandas to people The payoff is a revolution in medical research, leading the way to cures and treatments for a wide range of troublesome diseases.

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Tough Tobacco and the Petunia Boondoggle The RNAi epic begins in 1928 with, of all things, tobacco.

As published in the wildly popular Journal of Agricultural Research Journal of Agricultural Research , a scientist who infected a tobacco seedling with the deadly tobacco ring-spot virus didn't succeed in knocking it off (and this was years before we knew the evils of smoking). Try as he might, this researcher could not kill the plant with a supposedly deadly virus. Repeated infections had only a minuscule effect, shriveling the plant's bottom leaves. Wha . . . ? Why was it stubbornly thriving? What was protecting this tough tobacco? , a scientist who infected a tobacco seedling with the deadly tobacco ring-spot virus didn't succeed in knocking it off (and this was years before we knew the evils of smoking). Try as he might, this researcher could not kill the plant with a supposedly deadly virus. Repeated infections had only a minuscule effect, shriveling the plant's bottom leaves. Wha . . . ? Why was it stubbornly thriving? What was protecting this tough tobacco?

Fast-forward more than a half century and now the patient is a petunia. The protagonists are two plant researchers aiming to beef up the petunia's drab purpleness by giving it a scientific booster shot of color. In molecular-speak, they were supplementing the purple petunia with an additional pigmentation gene.

Well, it didn't work out. Adding this ”purpling gene” did not beef up the petunia's purpleness. Instead the puzzled plant scientists discovered that more is less less, and their gene-gineered petunia flowers were plain-Jane white, or at best, splotchy. The h.e.l.l . . . ? Why are the petunias white? What a boondoggle!5 Oblivious to the commercial windfall of dye-ready petunias, the curious researchers plodded on, searching fruitlessly for a reason behind this perplexing failure.

Smashed Dogma?

The frustrating dilemma in both instances was that the results seemingly violated scientific dogma, firmly established before we were born!

Math-religion guru Gregor Mendel worked alone in his bucolic monastery, making history with simple equipment available to any 1800s gardener. Mendel deciphered the rules for how genes from two pea parents combine, then transmit traits to their offspring. Today, Mendelian genetics explain why your hair is as frizzy and unruly as your mother's and her father's.

Mendel's laws form the basis of modern genetics and are the motive behind today's $40 billion biotech industry. But the petunia just didn't fit. The experimental results did not follow Mendel's laws. Oh no-sies! Talk about a fast track to career failure.

But it was not quite as intractible as an NP-Complete problem.6 The answer arrived, although it took its own sweet time. This time, it is the 1990s and a new set of researchers are focused on the age-old mystery, ”How do genes drive muscle development in roundworms as they grow in a petri dish?” The answer arrived, although it took its own sweet time. This time, it is the 1990s and a new set of researchers are focused on the age-old mystery, ”How do genes drive muscle development in roundworms as they grow in a petri dish?”

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The worm scientists' plan was to use a biotech trick to wipe out a particular worm muscle gene and witness what happens to the worms without that gene. But the scientists ran into a snag. Results were the opposite of expected! Adding a ”control blank” (RNA that was supposed supposed to do nothing) also wiped out the gene. Arghhh. What in tarnation was going on? to do nothing) also wiped out the gene. Arghhh. What in tarnation was going on?

This time, perseverance paid off. A series of carefully planned tests explained the impossible result and finally unveiled the workings-mechanism, gears, and cogs-of gene silencing. It was RNAi. It was RNAi. Earning the 2006 n.o.bel Prize for their work, Dr. Andrew Z. Fire and Dr. Craig C. Mello revealed that RNA itself, folded into a double-stranded knot, was the trigger for RNAi to shut down specific genes. Earning the 2006 n.o.bel Prize for their work, Dr. Andrew Z. Fire and Dr. Craig C. Mello revealed that RNA itself, folded into a double-stranded knot, was the trigger for RNAi to shut down specific genes.

Now it all made sense.

RNAi to the Rescue: Making Sense of Petunias In the Case of The Purple Petunia, the purple pigment gene would would have obeyed Mendel's rules, but that gene was being ignored: Its RNA messenger had been have obeyed Mendel's rules, but that gene was being ignored: Its RNA messenger had been chopped into bits chopped into bits by RNAi. In the Case of The Virus-Resistant Tobacco, RNAi by RNAi. In the Case of The Virus-Resistant Tobacco, RNAi diced up diced up the menacing ring-spot virus, a virus that otherwise would have stunted and killed the plant. the menacing ring-spot virus, a virus that otherwise would have stunted and killed the plant.

Molecular biologists are now convinced that RNAi protects things that can't run away, like a tobacco plant. But they are less clear on the biological reasons for RNAi to exist in mammals, including us. One theory-backed by a mounting a.r.s.enal of evidence-is that RNAi serves as guardian of our genome by restricting the philandering of traveling viruses and other mobile segments of DNA that might go cavorting from one place to another. Genes in the wrong place create big messes-including many diseases-and RNAi may be our body's way of keeping things tidy.

RNAi: Guardian of Our Genome RNAi: The gene broom, sweeping away suspicious fragments of RNA.

Imagine! What might RNAi be enlisted to do?

Imagine how many wonderful things we can do with a tool that destroys target genes!

Scientists are learning to use RNAi as a tool to eliminate the genes we dread, in tumors, diseased cells, HIV infections, and so forth. Imagine RNAi used as a specific and safe natural pesticide! Imagine custom RNAi sprays that eradicate crop infections slaughter mosquitoes, or make tastier lettuce! And admit it, couldn't lettuce use a tasty-spray?

Maybe it's time to revisit the purple petunia.

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REFERENCES:.

D. Baulcombe, ”RNA silencing in plants (Review),” Nature Nature 431 (2004), 356 -363. 431 (2004), 356 -363.

National Inst.i.tute of General Medical Science, ”RNA interference fact sheet,” mon fast track to a Darwin Award. We lead off with two stories regarding scatology, follow up with two rare ”living winners,” and end with four suspicious s.e.x acts. Darwin delivers well-deserved kudos to the creatively kinky!

Dying to Go * Short Circuit * m.u.f.fled Explosion * Bitter Biter Bit a Nitwit * Bench Press * Pipe Cleaner * Single Bud Vase * Battered Sausages

Also see Tennessee Pee, p. 184, and Rub the Mint, p. 199.

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Darwin Award Winner: Dying to Go Confirmed by Darwin Featuring urine, alcohol, and falling!

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