There is a nice post by Coffee Mug at Gene Expression on non-coding RNAs (ncRNAs). This post was provoked by a paper in Annual Review of Neuroscience. In light of my post on the recent Eric Lander and David Spector's talks, here's a snippet:
There are more ncRNAs than you thought:
- Half of the "full-length long Japan" library of human cDNA clones appear to be non-coding. Anti-jargon: cDNA (complementary DNA) is sequence read off of RNA backwards. This group tried to take a very large scale unbiased picture of the RNAs floating around in human cells and did bioinformatics to guess whether they coded for protein or not.
- The FANTOM 3 consortium sez that 62% of the mouse genome is transcribed. Half of these transcripts are non-coding.
- MicroRNAs are a subset of ncRNAs that regulate other RNAs. 70% of microRNAs can be found in the brain. There's a big section in the review on particular brain-specific miRNAs and potential roles in development.
- There are seven brain-specific small nucleolar RNAs (snoRNAs). These are RNAs that act as enzymes to chemically modify nucleotides in other RNAs. There is a particularly provocative connection between snoRNAs and serotonin receptor subtype processing in Prader-Willi Syndrome, a form of mental retardation arising from deletion of a chunk of chromosome 15.
- LINE-1 retrotransposons make up 17% of the human genome. These are the so-called "jumping genes". They code for the proteins to reverse transcribe them back into the genome. So it's relatively easy for them to proliferate. Technically they aren't non-coding, but the RNA is used in a nontraditional way in that it serves as a template for reading the gene back into the genome at some point. There is some evidence for a role for active LINE-1s in neural differentiation.
Maybe we're RNA beasts after all.
(P.S. I'm not sure about "62% of the mouse genome is transcribed. Half of these transcripts are non-coding." as only about 2% of the genome contains open reading frames ...)
- Log in to post comments
Ni Hao! Kannichi Wa!Touting all these non-coding RNA's as functional sounds somewhat like an Intelligent Design argument, the big designer in the sky created everything efficiently for a purpose.The bulk of RNA lying around is probably evolutionary junk left over from the extensive trial and error products off the genome to find something coding for a useful protein to survival.Anything with hybridizability back with DNA and RNA and mimics thereof can create enticing biological response artifact.I wouldn't doubt as detection goes down to single molecules with minimal lifespan, we will find that a product of about every conceivable segment of a gene greater than three base pairs can be combined to make an RNA.This fiddling around is how nature came up with a full length useful coding RNA. There wasn't much selection pressure to get rid of the failures.MOTYR
MOTYR,
I agree, lots of the RNA identified probably has no function. I guess the real question is how much of the transcribed stuff is junk. Of course proving a negative is very hard. But there definately are ncRNAs with some biological significance. In the past year, I've attended many talks where some weird ncRNA was pulled out of a screen and whose KO had dramatic effects. The number of these can't be 60% of the genome, but there are likely many more of these.
I think I do not agree at all. IF the primary function of many ncRNAs is to regulate translation you would potentially need an astonishing array of diversity of sequences to achieve specificity for repression or transport (as in the case of BC1 and FMRP or dsRNA binding proteins like staufen)or both. I understand that is a big IF, but I think it is supported by the current evidence. Moreover, the high degree of conservation of sequence in many regions of "junk DNA" does not support the hypothesis of "fiddling around" with non-coding regions for the use of generating new transcripts that will be translated. My 2 cents.
I imagine we have only begun to discover what RNA does in the cell.
PS the picture on the side bar kind of looks like a spider eating its prey. :)
That's the awesome power of microtubules.
"Living in an RNA World" would make a good name for a pop song.
Have you seen the paper in this week's Science on a ribozyme encoded in an intron of the CPEB3 (of Erik Kandel fame) gene? Quite interesting. Too bad they didn't have the space to speculate too much on the implications of a ribozyme smack in the middle of an important LTP IEG. I'd have loved to hear that one!
Thanks for the heads up, I have yet to peruse the latest papers.
i know its too late and no one will read this, but i'd like to point out that CPEB should really be of Joel Richter fame. Kandel made one provocative discovery and pimps it. Joel Richter figured the whole damn system out and continues to do good work on it.