> > Here's one for Ian. He is curious about Pat's ideas on the "purpose"
> > and intentions of RNA.
> > During a conversation about teleology, I was insisting that the
> > universe is basically devoid of purpose, whilst Pat was pointing out
> > his theory that everything is connected by a vast Quantum god, and
> > affects the world with a string theory model, in which He is
> > demonstrated to be Omniscient, omnipresent and omnipotent. It seems
> > that RNA is the main areas in intervention.

> > Some quotes to give you the fell of the discussion:

> > >For all we know, RNA could be using their hosts for experimenting.
> > > Whilst it may sound silly, we know that, at the root level, it's RNA
> > >that's calling the shots.
> > > LOL!!  RNA rules.  And you're living proof.  I couldn't care less
> > > what you think, Chaz.  RNA runs our machinery.

> > I excused myself from the discussion, thinking it to whacky, and
> > wanting to avoid the inevitable insults that were queueing up in my
> > language processor.

>      Rather, to give you one side of it.  Later, of course, Chaz comes
> out with this one:

> "The raison d'etre of the gene is to make an organism that survives."

>      If he wants to have his cake and eat it too, that's fine by me.

>    Also, to set the record straight, in the above passages he's
> cobbled together and removed the context.  I had also put a link in to
> an article entitled: When RNA Rules.  Here's the TEXT of that article
> (if you want to find it, Google "RNA rules" and look for 'Whitehead
> Institute'.  It was the sixth link when I did it.):

>  When RNA rules

> A newly discovered class of molecules plays an astonishingly powerful
> role in biology

> What do newly discovered molecules called microRNAs and the Internet
> have in common? Both reshaped entire fields in the past decade, says
> Whitehead postdoctoral fellow Andrew Grimson.

> “That’s a fairly grandiose claim for microRNAs,” acknowledges Grimson,
> who studies them. “But the discovery of the widespread role of these
> molecules changed the landscape of biology very quickly.”

> “Labs across the world, working on a variety of biological questions,
> are now integrating microRNAs into their research,” says David Bartel,
> Whitehead Member and Howard Hughes Medical Institute investigator.

> Bartel and his colleagues have helped to fuel the frenzy by
> identifying hundreds of the small RNA molecules and providing
> compelling evidence that they regulate the production of thousands of
> proteins in plants and animals.

> “Computational work has produced a very big picture of what microRNAs
> are likely to be doing in a very short time,” says Nobel laureate and
> MIT Institute Professor Phillip Sharp.

> Until the early 1990s, no one had a clue about microRNAs, which flew
> under the radar because of their tiny size. Each one contains only 21
> to 24 nucleotides, or letters of the genetic alphabet, so scientists
> simply missed them. Victor Ambros’s group found the first microRNA—
> lin-4—in 1993 at Harvard Medical School while studying a mutation in
> the worm Caenorhabditis elegans.

> Another Harvard researcher detected a second microRNA in 2000. One
> year later, the floodgates opened with the discovery of nearly a
> hundred in worms, insects and humans. At this point researchers began
> calling these tiny regulatory molecules “microRNAs.”

> The discoveries changed conceptions of RNA. Scientists have known for
> decades that RNA molecules serve as messengers and translators,
> building proteins from DNA sequences. But microRNAs determine which
> DNA sequences get translated in a given cell, a responsibility once
> considered the purview of proteins known as transcription factors.
> MicroRNAs essentially choreograph biological ballets, helping to
> determine where and when proteins can appear to perform. Thus RNA can
> add “regulator” to the roles listed on its résumé.

> MicroRNAs bind to messenger RNAs that code for proteins involved in
> activities ranging from development to cancer, and disrupt the
> production of these proteins. In humans, microRNAs regulate roughly
> one-third of protein-coding genes, and that’s a conservative estimate.

> Going through the genome
> “This is the first discovery of a broad biological mechanism that’s
> been made since genomics,” says Nobel laureate Phillip Sharp, who is
> investigating how microRNAs work at MIT, where he is an Institute
> Professor.

> Scientists determined the scope of microRNA activity in a matter of
> years by mining recently published DNA sequences. Bartel, an RNA
> biochemist, and computational biologist Christopher Burge of MIT
> played a leading role. They collaborated to develop computer programs
> that scanned genomes to identify microRNAs and their messenger RNA
> targets. Their work helped to ignite interest in microRNAs as
> biologists in labs around the world realized the tiny molecules
> regulate a large portion of the protein-coding genes in plant and
> animal cells.

> “Computational work has produced a very big picture of what microRNAs
> are likely to be doing in a very short time,” says Sharp. “ “It feels
> like the field is moving at warp speed,” agrees Burge, a Whitehead
> Career Development Associate Professor of Biology. “Genomic approaches
> have provided a number of important insights, and there has been nice
> synergy with molecular and biochemical studies.”

> Finding the first microRNAs
> Rosalind Lee and Rhonda Feinbaum, researchers in the Ambros lab, were
> conducting painstaking experiments on C. elegans when they bumped into
> the first microRNA.

> They knew that early development of worm larvae required proper levels
> of the novel protein lin-14. They also knew that something was
> regulating those levels and assumed it was another protein, so they
> set out to isolate the gene for that protein. The result amazed them.

> The gene fell on a stretch of DNA once termed “junk” by some, a
> stretch outside the protein-coding region of the chromosome. It
> appeared to code for a small RNA molecule— lin-4—that somehow
> regulated lin-14 levels.

> The researchers wondered if lin-4 was an esoteric molecule or a
> harbinger of a new class of RNAs. “We had no basis for saying that
> lin-4 was part of something much broader,” says Ambros, who now works
> at Dartmouth Medical School.

> His lab had no luck searching for additional RNAs in the next few
> years. He was thrilled when researchers in the lab of Harvard Medical
> School’s Gary Ruvkun discovered another gene in C. elegans that coded
> for a small RNA called let-7 in 2000. In addition to cloning let-7,
> Ruvkun’s group examined the genomes of a number of other animals and
> found the gene for let-7 in most of them. The study foreshadowed the
> role of genomics in later research.

> In 2001, Rockefeller University associate professor Thomas Tuschl
> (formerly a postdoctoral fellow in the Bartel lab), Ambros and Bartel
> independently found dozens of additional small RNA genes in worms,
> flies and humans and decided to call them microRNAs.

> Leveraging genomics
> Bartel realized he needed to look outside the toolbox of classical
> biology. In 2001, he approached Burge—who had previously developed
> algorithms to identify protein-coding genes in the human genome—and
> Lee Lim, who had just completed his PhD training with Burge. The
> researchers jumped at the chance to explore a new class of genes. Lim
> worked jointly with the two labs to write a computer program that
> could scan DNA sequences and predict microRNA genes.

> He started by examining known microRNAs. Each microRNA is generated
> from a piece of RNA that folds back on itself to form a structure that
> resembles a hairpin. Lim scanned the genome of C. elegans for DNA
> sequences that would give rise to hairpins after being transcribed
> into RNA. He then looked for ways to further refine the search.

> The double-stranded RNA of a hairpin is chopped and processed into a
> single-stranded microRNA by proteins called Drosha and Dicer. But
> apparently these proteins don’t recognize every hairpin. Lim whittled
> down the list of potential microRNAs by eliminating DNA templates for
> hairpins that lacked Dicer-friendly characteristics.

> Lim then screened the remaining microRNA candidates by comparing the
> genomic sequence of C. elegans with that of the related worm C.
> briggsae. He reasoned that most of the genuine microRNAs, those
> performing critical biological functions, would be conserved across
> species.

> Eventually, the team showed that the human genome contains more than
> 200 microRNA genes. “We were excited to find new microRNAs,” says
> Burge. “But then the big question was—what do they do?”

> This question had been largely answered in plants. Matthew Jones-
> Rhoades, a graduate student in the Bartel lab, had discovered that
> plant microRNAs have extensive and highly conserved pairing to plant
> messenger RNAs, so he could easily identify many targets of the plant
> microRNAs.

> “At a time when we had about 50 plant targets, we were still in the
> dark regarding which genes were targeted in animals,” says Bartel.

> Benjamin Lewis, a graduate student in both the Bartel and Burge labs,
> developed a second computer program to bridge this gap. He took the
> sequences of known micro-RNAs, scanned animal genomes for
> corresponding messenger RNA targets and, like Lim, used conservation
> across species to screen the results. The goal was to find many more
> conserved microRNA-mRNA pairings than would result by chance. But the
> initial program failed to deliver.

> The researchers then tried another twist. Previous work showed that
> some microRNAs pair only partially with their mRNA targets, so the
> team hypothesized that one part of each microRNA sequence might be
> particularly important. They were right. Lewis hit the jackpot when he
> required perfect

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