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)"

Comments

Science

[Mozk]

This is how science evolves. One theory revises another. At least they're willing to say they they were wrong, unlike hundreds of years ago.

Re:Science

[Salis]

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.

Re:Science

[Anonymous Coward]

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...

no pun intended

[Anonymous Coward]

All your base are belong to RNA.

Too Bad...

[xski]

Is everything we know about genetics off-base? (no pun intended)

I thought it was a great pun.

I suspect so but didnt know for sure

[taj]

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.

so DNA->RNA->Protein

We could work with DNA we could work with most protiens. RNA? no way. well sortof but.. no way.

So DNA and Protein do play major rolls no doubt. but we could not get an angle on the RNA. 1990's tech.

Re:I suspect so but didnt know for sure

[mlush]

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.

oh good lord

[CupBeEmpty]

ok as someone that works in this field let me say this:

RNAi is a very useful tool, but this is definitely several years behind the curve. RNA has been shown to regulate much more than previously thought. However talk about "the secret world of RNA" is pretty much like claiming that there is a "secret world of open source software." Neither one is very secret or very new.

The biggest contention I have is this quote from the article: "This knack of completely eliminating a protein makes RNAi a valuable research tool." This is wrong, because RNAi does not work like this at all. This is actually one of the drawbacks to using RNAi to eliminate proteins. It does not eliminate, it reduces. To get rid of a certain protein, the classic method is to completely remove the DNA that codes that protein from the organism studied. This is referred to as a "knock out" because the organism has no ability to make that proteind from the removed DNA. RNAi however, provides only a "knock down" because the DNA is still there and no matter how much RNAi is used there is still some expression of the protein. Also, many RNAi protocols are transient supressors not permanent knock outs of protein.

So basically this is an exciting new field but don't necessarily believe all the hype because this is no miracle answer. The article is good, but oversimplified.

C'mon

[Otter]

Is everything we know about genetics off-base?

It's worth noting that the field of "genetics" precedes even the identification of DNA and RNA. It may be that what we now know about gene regulation is wildly incomplete (although even that is unlikely, although possible) but Mendelian genetics is completely agnostic as to whether "genes" are protein-coding or not.

Damn registration. Here is recent similar article

[zymano]

http://www.sciencedaily.com/releases/2005/09/05090 6081607.htm

Re:mRNA is fascinating stuff...

[RyanFenton]

Nah - iRNA is a subset of mRNA (see your link), which is all a subset of RNA. mRNA is so fascinating to me because of the ranges of messages that can be sent, and what all those interactions really mean. So far it seems that various kinds of mRNA, not just iRNA can be used ultimately to manipulate DNA on and off to help us see what the whole of DNA ultimately can functionally mean.

Again, I'm just a layman on the issues - and find it deeply fascinating in terms of the pure science of it.

Ryan Fenton