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RNA May 'Run' Genetic Coding

leonbrooks writes "First a Stanford Medicine Magazine article speaks about RNA 'produced by plants that turn genes on and off', and now a Science Magazine issue says 'For a long time, RNA has lived in the shadow of its more famous chemical cousin DNA and of the proteins that supposedly took over RNA's functions in the transition from the 'RNA world' to the modern one. The shadow cast has been so deep that a whole universe [of RNA] has remained hidden from view, until recently' and speaks of 'an order of magnitude more transcripts than genes', suggesting that more actual coding is done through RNA than DNA. Is everything we know about genetics off-base? (no pun intended)"

19 of 168 comments (clear)

  1. Re:Science by Salis · · Score: 4, Informative

    It'll more likely be translational control via RNA.

    RNA can quickly hybridize with regulatory regions of mRNA and change their translation rate.

    And these RNA transcripts can be very small, but still regulate the translation of many genes. It'll be a while until the function of all of these RNA's are understood.

    --
    Favorite /. tagline: "On the eighth day, God created FORTRAN." And it was good.
  2. Re:Uh... by ip_fired · · Score: 2, Informative

    Well, what you described was the normal job of RNA. According to the article, RNA also has the ability to block proteins, and also turn off specific genes.

    They state that it has opened up many possibilities in finding out which gene does what. They mention that they have successfully used this technique to stop the spread of some diseases, like Hepatitis B and it could possibly lead them to discover more about cancer.

    Read the HTML article, it is very interesting and informative for anybody who is interested in genetics.

    --
    Don't count your messages before they ACK.
  3. mRNA is fascinating stuff... by RyanFenton · · Score: 2, Informative

    Speaking just as a layman, mRNA is truly a fascinating subject

    Using it, many, many parts of DNA can be turned off, and countless experiments can be done to find out exactly how we work. mRNA seems to be the scientific advancement we needed to spark the next revolution in the understanding of our most basic mechanisms. It is by turning things off that we can see most of what was hidden to us this far.

    Already, it has some medical use, in reducing the further damage of macular degeneration caused by excessive production of blood vessels in the eye. And it's only just begun.

    There's a lot of justified hype here. But so long as it can allow for real progress of science, I'll be happy - research in general needs some general PR on the public stage. Hopefully private and public interest in general research could at least be put in a positive trend for a while at least.

    In the words of the fictional "MC Hawking", what we need more of is science.

  4. Short Interfering RNAs by Anonymous Coward · · Score: 3, Informative

    The article is referring to short interfering RNAs (aka micro RNAs), which exert their effect post-transcriptionally (i.e., they are not involved in 'coding' as the summary suggests, but rather in suppressing the expression of 'coding' mRNAs that have already been produced via transcription).

    It is not that what was previously known was 'wrong'; RNAi is just an additional (and important) layer in the regulation of gene expression beyond what was previously recognized.

  5. Re:RNA World? by nathos · · Score: 0, Informative
    Anybody know what's meant by the "RNA world" term? I'm not sure if this is correct or not, but is that the theory where pre-cellular life used purely RNA for all functions?

    Yes, precisely. It's postulated that RNA was the transitional link between non-living chemicals and living organisms with DNA. Even today, the simplest of organisms (viruses) use only RNA to carry their genetic information.

  6. No subscription to Science mag online? No prob... by Veenix · · Score: 3, Informative
    For those of you without a subscription to Science magazine online, here's an amusing solution - Coral Cache, since NYU has basically a subscription to all academic publications :)

    http://www.sciencemag.org.nyud.net:8090/cgi/conten t/summary/309/5740/1507?rbfvrToken=bba41c737e9d32e 852952029f4e32998530ff0d1

  7. Re:no pun? by djupedal · · Score: 3, Informative

    Puns, as anyone who understands the concept of this particular type of humor knows, generally fall into two categories: obvious and subtle.

    In the case of an obvious pun, the tag line has come to be expected, and functions as a means of self-effacement, which is a respected attribute in many cultures. "Oh, wow...look...I just made a funny! I hope everyone appreciates the serendipitous nature and doesn't think I wrote the entire paragraph just for that purpose...? Honestly, it was just luck!"

    Then of course, you have the punster who, fearing that their efforts at humor will go unappreciated, use such a tag to help focus/force attention on their autoring prowess, and thereby increase the overall audience. Leave no laughter behind...

    In the case of 'i hate when ppl say...', most agree that this is simply an act of jealousy, where the childish hope is a dig will get them part of the (positive) attention as well, when, in fact, it usually warrants little more than pity.

    In those cultures where punning is a part of daily life, intended or not, such gestures should be encouraged, not derided, since they help us to identify with others, while allowing us to show our individual ability to give and take - aka share.

    Try living in a culture where the pun is non-existent. Conversations become boring rather quickly, and you have to find less elegant means of making a point. Some learn alternate means of expression, and some find it just too much work, and then become nothing but spectators. Personally, I find being able to use a pun means being able to craft better conversations, and I hate it when people don't 'get it'...

  8. Damn registration. Here is recent similar article by zymano · · Score: 4, Informative
  9. HIVD by Ieshan · · Score: 2, Informative

    25% of HIV patients (according to Squire et al, 2003; see also Budka, 1991) develop HIVD, HIV-Dementia Complex.

    Macrophages become distributed throughout deep grey and white matter structures (such as the Amygdala).

    Theory 1: Retroviral envelope proteins are cytotoxic (and neurotoxic).
    Theory 2: Neuronal degregation is caused by macrophage factors associated with AIDS and HIV.

    I'm not sure it has anything to do with "facilitation of transmission". It may be a resultant of random processes caused by the virus.

  10. TFA by Anonymous Coward · · Score: 1, Informative

    Science, Vol 309, Issue 5740, 1507 , 2 September 2005
    [DOI: 10.1126/science.309.5740.1507]

    Introduction to special issue

    In the Forests of RNA Dark Matter

    Guy Riddihough

    For a long time, RNA has lived in the shadow of its more famous chemical cousin DNA and of the proteins that supposedly took over RNA's functions in the transition from the "RNA world" to the modern one. The shadow cast has been so deep that a whole universe (or so it seems) of RNA--predominantly of the noncoding variety--has remained hidden from view, until recently.

    Nor is RNA quite so inert or structurally constrained as its cousin; its conformational versatility and catalytic abilities have been implicated at the very core of protein synthesis and possibly of RNA splicing. Noller (p. 1508) discusses how the basic building block of RNA--the double helix--has been fashioned into the intricate "protein-like" three-dimensional surfaces of the ribosome. A further parallel between RNA and protein is revealed in the structure of an RNA group I self-splicing intron, which uses an arrangement of two metal ions for phosphoryl transfer much like that seen in many protein enzymes (p. 1587). Another group I-like intron catalyzes the formation of a tiny RNA lariat, a reaction strikingly similar to one seen in group II introns and spliceosomal introns (pp. 1584 and 1530). This unusual lariat, at the very 5' end of the resultant mRNA, is suggested to help protect the mRNA from degradation. The dynamics of the RNA messages passed between nucleus and cytoplasm provide a complex and sophisticated layer of regulation to gene expression, covered by Moore (p. 1514), who describes the teams of proteins that escort and regulate mRNA throughout the various stages of its life (and death). Death for many mRNAs occurs in cytoplasmic foci called P-bodies, which can also act as temporary storage depots for nontranslating mRNAs (see the Science Express Report by M. Brengues et al.).

            Figure 1
            CREDIT: A. Baucom and H. Noller

    Small noncoding microRNAs (miRNAs) have been found in such abundance that they have been christened the "dark matter" of the cell, a view reinforced by an analysis of the small RNAs found in Arabidopsis (pp. 1567 and 1525). The role of miRNAs and of their close cousins small interfering RNAs (siRNAs) in RNA silencing is discussed by Zamore and Haley (p. 1519), and illustrated in the poster pullout in this issue and in research showing that miRNAs can repress the initiation of translation (p. 1573) and, intriguingly, can also increase mRNA abundance (p. 1577). [See also this week's online Science of Aging Knowledge Environment (SAGE KE) and Signal Transduction Knowledge Environment (STKE)]. The phrase "dark matter" could well be ascribed to noncoding RNA in general. The discovery that much of the mammalian genome is transcribed, in some places without gaps (so-called transcriptional "forests"), shines a bright light on this embarrassing plentitude: an order of magnitude more transcripts than genes (pp. 1559, 1564, and 1529). Many of these noncoding RNAs (p. 1527) are conserved across species, yet their functions (if any) are largely unknown: A cell-based screen shows one, NRON, to be a regulator of the transcription factor NFAT (p. 1570). Of course, in some cases it is the act of transcription that is the regulatory event, as in the case of the transcriptional regulation of recombination (p. 1581). Finally, even the coding and base-paring capacity of RNA can be altered--by RNA editing, in which bases in the RNA are changed on the fly. Analysis of editing enzymes (p. 1534) reveals that the cell-signaling molecule IP6 is required for their editing activity.

  11. Re:WTF? by alicenextdoor · · Score: 2, Informative

    Of course RNA can code for more than DNA does: RNA editing, where the RNA sequence itself is modified after transcription; differential intron splicing, where different bits are cut out of the pre-mRNA to form different forms of mRNA. Then there's post-translational modifications to the proteins themselves... A single gene can produce dozens of different proteins (there's one expression in brain tissue which produces around 900 different proteins, but I don;t recall its name) many of which can be completely different from each other. Not to mention functional RNAs themselves. The human proteome probably contains hundreds of thousands of proteins. So yes, it all comes from DNA, but RNA is more than just an intermediary.

    --
    of course, biting monkeys is not to everyone's taste - Konrad Lorenz
  12. Actually... by Zouden · · Score: 3, Informative

    It's Kary Mullis, and he made an absolute fortune from PCR. The patent on Taq-pol is one of the most valuable patents ever.

    Secondly, you should be modded down for copy-and-pasting that diatribe against HIV/AIDS which is quite off topic.

    And while Kary Mullis made a brilliant discovery (PCR) he came up with it while he was stoned (no joke). This explains a lot of his unconventional theories...

    --
    "A week in the lab saves an hour in the library"
  13. Re:I suspect so but didnt know for sure by mlush · · Score: 5, Informative

    RNA is the hardest to work with in the laboratory. It just fall to pieces. When I was working with DNA/RNA/protien it was just really hard to work with RNA.

    I'd disagree, sure RNA is fragile and falls apart at the drop of an RNAse (1), but its chemically uniform, one batch is pretty much like the next and there are plenty of commercial protocols and reagents for manipulating it.

    Working with RNA really a matter of good technique (paranoid levels of cleanness and make sure all reagents are free of RNAse). If I had a sample of RNA that coded myosin, a sample that coded for pepsin and a sample of total RNA (all the different RNA molecules in a cell). I can use exactly the same methods to purify and study them.

    Protein on the other hand is a pit of horrors, the thing is that every protein is different, what works with one protein will completly degrade another, some proteins are so unstable that they degrade with time even under perfect conditions, some are so rare that there may only be 2-3 molecules in a cell. With RNA there are thousands of labs and really BIG money working on essentially the same molecule, with protein you may be the only person ever to study it

    (1) RNAse is the bugbear of RNA work, its a normal part of every cell and its job it to break up RNA (which it does very well). When its in the cell its kept under close control, however if the cell is broken up (to extract RNA for example) the control is broken and it eats any RNA it can find. When prepareing RNA the first step it to break up the cells/tissue and inactivate the RNAse without damaging the RNA (not too hard there a strong solution of salts it used). The trouble is that RNAse is really really stable, you can spit in a testtube boil it for 10 minutes and the only enzyme still active is RNAse. When the salts are removed and RNA extracted, any RNAse contaminant will reassemble and eat the RNA.

  14. Re:some related genetics.. by Anonymous Coward · · Score: 2, Informative

    Wow, and I thought my background in circadian research would never be useful!

    A proposed schematic of the Drosophila's circadian system is illustrated here. In the associated paper, we basically created a mathematical model of the schematic using standard biochemical equations and harnessed the power of computers to test the model against results from actual "wet-lab" experiments.

  15. Role of RNA in Early stages of Evolution of Life by Aeternal · · Score: 3, Informative

    Commentators in this thread seem to have missed one of the main implications of the quoted article (this implication is not a new one anyway): Early organisms were functionally organised, and genetically coded for, by RNAs. DNA and proteins, including the catalytic functions of enzymes, came later. See the following, for example: "1: Nature. 2002 Jul 11;418(6894):214-21. Related Articles, Links The antiquity of RNA-based evolution. Joyce GF. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. gjoyce@scripps.edu All life that is known to exist on Earth today and all life for which there is evidence in the geological record seems to be of the same form--one based on DNA genomes and protein enzymes. Yet there are strong reasons to conclude that DNA- and protein-based life was preceded by a simpler life form based primarily on RNA. This earlier era is referred to as the 'RNA world', during which the genetic information resided in the sequence of RNA molecules and the phenotype derived from the catalytic properties of RNA."

  16. Re:Science by Anonymous Coward · · Score: 5, Informative

    There is much more to that already.

    It is widely known that small RNAs can regulate translation of mRNAs by binding to them in the context of specialized protein complexes (e.g. RISC) but they can also target these same mRNAs for degradation or impair their production in the first place by blocking transcription.

    I believe that you are refering to microRNAs (although there are many other types).
    MicroRNAs are commonly thought to control expression of cognate mRNAs only by inhibiting their translation but that is far from being the actual case. In fact, while this may be a common trend among the characterized microRNAs from animals, most plant microRNAs act by degrading the target mRNAs. In addition, a recent letter to Nature pointed that many microRNA targets in animals may be degraded in the process: http://www.nature.com/nature/journal/v433/n7027/ab s/nature03315.html
    (sorry, subscription only)

    Furthermore, there is clear evidence from plant and yeast species that small RNA molecules can regulate the structure of chromatin (the bundles of DNA and histone proteins which constitute the chromosomes themselves). By regulating the status of chromatin you can also regulate the expression of the underlying genes. It is still not clear if the same happens in animal cells...but it is possible (and many say likely).

    This adds to three different levels at which small RNA molecules can regulate the information flow from DNA->RNA->protein and we are just scratching the surface since most of these small RNAs and their targets are still being discovered (by the hundreds).

    The funny thing is that until 1998-99 these small molecules (20-40 nucleotide long) were simply dismissed as junk...

  17. Re:Science by Anonymous Coward · · Score: 1, Informative

    He means that there are small RNA molecules in the cell that can recognize and bind (hybridize) to a messenger RNA (mRNA) and block it from delivery its information (translation).

    This means that these small molecules can interrupt the communication between the DNA code and production of specific proteins.

    Many of these small molecules are encoded in the genome and are produced by the cells in specific conditions. Researchers are combing the genome to find them and then identify their gene targets.

    I hope this is helps!

  18. Re:Left unanswered... by kronocide · · Score: 2, Informative

    Or maybe they are not usefully described in the computer program metaphor.

    DNA is not a program. For one, "program" implies that there is a fixed temporal order to the instructions. But organism development is initiated by cues from the environment, the order of execution is not stored anywhere. And its not even like subroutines, since what the DNA does is producing proteins. They are little machines that help to produce material substances when epigenetic mechanisms ask for them. The epigenome is more like a factory that produces according to information from the environment combined with its genetic capabilities than any sort of computer running a program. If you must view it as some turing machine, you need to include the whole environment, since much of the controlling information is "stored" there.

  19. Re:I suspect so but didnt know for sure by mlush · · Score: 2, Informative

    >> RNAse is the bugbear of RNA work, its a normal part of every cell and its job
    >> it to break up RNA (which it does very well). When its in the cell its kept under
    >> close control, however if the cell is broken up (to extract RNA for example) the
    >>control is broken and it eats any RNA it can find.
    >Darned DRM. You'd think I would at least have fair use rights over my own body!

    Don't sweat it, the binarys have DRM but the source code is freely avalable