Why RNA folding?

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Rhiju
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Message 37834 - Posted: 15 Mar 2007, 4:35:55 UTC

Rosetta@home has been used to predict protein structure and design new
proteins. Improving protein enzymes that process carbon dioxide,
designing a protein vaccine for HIV, and understanding the basic
physical principles underlying protein folding are all being carried
out in the workunits that you are currently running or will be running
in the near future. Why study this other biopolymer, RNA?

Indeed, for a long time, RNA was mainly thought of as a passive
messenger in the cell, sort of a temporary copy of DNA (the storehouse
of information in our cells) from which proteins were translated. That
view changed dramatically in the 1980s with the discovery that RNA can
do more than carry information -- it can fold up into intricate
stuctures and carry out chemical reactions, just like proteins can. In
fact, its ability carry out the function of both DNA and proteins
provide a convenient answer to the chicken-and-egg problem of how
proteins and DNA evolved ... RNA came first! For more on the RNA
world
, see
Wikipedia,
for example.

In addition to being important in early life, the known roles of RNA
in our present cells are currently exploding. From small RNAs
(\"Breakthrough
of the Year\"
in Science in 2002, and the subject of last year\'s
Nobel
prize winning work
) to the catalytic heart of the ribosome, RNAs
play fundamental roles in biology that go beyond merely passing
messages. From a medical standpoint, most antibiotics target RNA in
the ribosome; the genomes of HIV, SARS, and other retroviruses are
composed of RNA; and RNA \"aptamers\" are beginning to be used as easily
evolvable drugs.

With Rosetta, we are making a serious stab at solving one of the most
fundamental puzzles for this interesting molecule... how RNA
folds. We\'re starting small, though some of the molecules you\'ll see
on our screen are important pieces of HIV. The hope is that we\'ll be
able to soon predict the folds of bigger RNAs -- a challenge that is
all the more important because RNA structures are difficult to solve
experimentaly. In the further future, using these structure prediction
tools to design or enhance ribozymes (that is, RNA enzymes) for
medical therapy is not that far-fetched ... stay tuned!




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hugothehermit

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Message 38467 - Posted: 27 Mar 2007, 6:04:22 UTC
Last modified: 27 Mar 2007, 6:05:14 UTC

Please tell me of I\'m wrong, but does this mean that:
1. A folded RNA could/does act as a protein chaperon?
2. Can a folded RNA correctly translate a protein, or perhaps I should say that can a mis-folded RNA not fold the correct protein?

This adds a huge amount of complexity, just when I thought I was getting a handle on things :?

I was beginning to think, that the lack of chaperon proteins was the cause of protein mis-folding, but now it may be incorrectly folded RNA.

Even though I am confused, you\'ve got to marvel at the beauty of nature don\'t you, using RNA as both a DNA carrier and as a protein is a nice touch [I doff my cap to nature]
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Rhiju
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Message 38536 - Posted: 28 Mar 2007, 20:40:09 UTC - in response to Message 38467.  

Hi Hugo:

Sorry for the late reply, we\'re in the midst of a lot of code development! To my knowledge, there\'s not much evidence for RNA\'s interfering or chaperoning protein folding in the modern day, though thay may well have been the case in the past; its also a largely unexplored area, so stay tuned to discoveries over the next few years.

As for the second question, messenger RNAs curled up into folds are generally thought to be unraveled by the ribosome and its associated helper proteins (e.g., \"helicases\") before translation occurs. However, there are several known cases -- probably just the tip of the iceberg -- where folds in the RNAs do change how translation occurs. In one example, an RNA forms an ornery pseudoknot (look on your screen for 1l2x!) that appears to pause the ribosome for a little bit and causes a so-called frameshift. The messenger RNA is translated then as,. e.g. ACG/ACG/ACG... instead of CGA/CGA/CGA... Its a neat trick used by these viruses to encode up to three protein sequences in one RNA.

Part of my (long-term) plan is to understand what folds (if any) are potentially formed by generic messenger RNAs in our cells before they encounter ribosomes -- its largely an unexplored question!

Please tell me of I\'m wrong, but does this mean that:
1. A folded RNA could/does act as a protein chaperon?
2. Can a folded RNA correctly translate a protein, or perhaps I should say that can a mis-folded RNA not fold the correct protein?

This adds a huge amount of complexity, just when I thought I was getting a handle on things :?

I was beginning to think, that the lack of chaperon proteins was the cause of protein mis-folding, but now it may be incorrectly folded RNA.

Even though I am confused, you\'ve got to marvel at the beauty of nature don\'t you, using RNA as both a DNA carrier and as a protein is a nice touch [I doff my cap to nature]


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Message 71303 - Posted: 21 Sep 2011, 16:00:49 UTC
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Message 75886 - Posted: 2 Aug 2013, 6:06:40 UTC

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Message 76293 - Posted: 16 Dec 2013, 6:38:39 UTC

Any of you who want RNA studied and don\'t mind beta projects with LONG workunits (often a few months) may be interested in another BOINC project already doing such studies:

RNA World (beta)
http://www.rnaworld.de/rnaworld/

They\'re finally getting around to adding checkpoints to their applications. Previously, running their applications meant you often had to keep your computer running continuously, with strong restrictions on any interruptions.
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Message boards : Rosetta@home Science : Why RNA folding?



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