here are a few more papers of interest:

Bartel, D.P., MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 2004. 116(2): p. 281-97

Krichevsky, A.M., et al., A microRNA array reveals extensive regulation of microRNAs during brain development. RNA, 2003. 9(10): p. 1274-81.

John, B., et al., Human MicroRNA targets. PLoS Biol, 2004. 2(11): p. e363.

Lu, J., et al., MicroRNA expression profiles classify human cancers. Nature, 2005. 435(7043): p. 834-8.

Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, Burge CB, Bartel DP. The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science. 2005 Dec 16;310(5755):1817-21.

Coffee Mug: “An issue that remains to be resolved is whether translational repression leads to P-body targeting and degradation or vice versa.”

P-body targeting and degradation of mRNA reminds me of the ubiqutin-proteasome pathway for protein degradation. Small signaling proteins can be targeted for rapid turnover. Old signal information is wiped away so that new signals control the system.

http://homepages.bw.edu/~mbumbul...uli/cell/ublec/

http://en.wikipedia.org/wiki/Ubiquitin


Here is a link to research on using RNAi techniques to build synthetic life tools.

http://openwetware.org/wiki/Main_Page

here's some of the old stuff:

Tomizawa, J., Itoh, T., Selzer, G., and Som, T. (1981) Inhibition of ColE1 RNA primer formation by a plasmid-specified small RNA. PNAS 78:1421-1425.

van, d.e.r., Mur, L.A., Beld, M., Mol, J.N., and Stuitje, A.R. (1990) Flavonoid genes in petunia: addition of a limited number of gene copies may lead to a suppression of gene expression. Plant Cell 2:291-299.

Fire, A. et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806–811 (1998).

Elbashir, S.M., Lendeckel, W., and Tuschl, T. (2001) RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev 15:188-200.

Will the guys that discovered this get the Nobel prize? Do you think they knew that themselves right away? Are they making any money off this?

oh i could see a nobel or two coming out of this.. i'm not sure how it will play out.. do the people who made the experimental observations get the prize or the people who realized what was going on?

there are a ton of siRNA design and manufacture startup companies and i know that at least Dharmacon was started by and is recruiting university folks that study it.

if you're really curious try looking up the board of directors of dharmacon, qiagen, invitrogen, ambion, and sirna and then lit-searching their names..

This post is interesting due to the fact that I actually have somewhat of a personal connection to some of this. In Fall 2004 I worked under a postdoc who was trying to determine what proteins were required for miRNA-mediated translational repression. The principal investigator of the lab in which we were working is an X-ray crystallographer whose wife is the corresponding author for the Dicer structure paper. Therefore I can say I have some connection to the field of miRNAs, though I am no longer working in it and probably will not return to it as the field is too young for theory to be of much use.

Also, the real-time comment viewing is neat.

http://www.eurekalert.org/pub_re...l- tla060806.php

"The discovery of piRNAs reveals a new dimension of the small RNA world. The complexity of piRNAs and their correspondence to different types genomic sequences implicates their potentially diverse functions. This is another gold mine for studying gene regulation, especially that related to reproduction and inheritance," explains Dr. Lin.
…
“While hundreds of small RNAs have been isolated from somatic tissues in mammals, these papers are representative of a number of recent and up-and-coming studies independently identifying unique small RNAs residing in the mouse germline. The newly identified piRNAs are bigger in size (26-31 nucleotides long) than most previously described small RNAs in mammals, and are shown to be associated with the piwi subfamily of the Argonaute protein family. They are largely expressed in the mouse testes, and are thought to play a role in spermatogenesis.

Future research will be aimed at elucidating the pathway of biogenesis of these novel, small RNAs, as well as the targets and function of this emerging class of molecules. Dr.Watanabe emphasizes that "Newly identified small RNAs have features clearly different from those of previously identified small RNAs such as miRNAs or siRNAs. The sequences of this novel small RNAs are not conserved between species. However, interestingly, the presence of this novel class of small RNAs is conserved among diverse animals including humans." “

It seems so wasteful to transcribe these sequences and then turn around and degrade them. What am I missing?

Perhaps when you add up all the ATP's involved here, they pale in comparison to the numbers you need for ordinary metabolism.

ken: “It seems so wasteful to transcribe these sequences and then turn around and degrade them. What am I missing?”

I don’t think anyone really knows but here are my guesses…

First, molecular turnover is normal in cells. Proteins are recycled with average times that vary from a few minutes to a few hours. (Proteins that can’t be recycled tend to accumulate and cause damage.) The recycling serves at least three purposes. The cell can adapt as needed. Miss-assembled or damaged proteins are replaced. Fast recycling of signaling proteins wipes the slate clean so that new signaling proteins control the cell.

Second, rather than needing a separate control system for each coding gene in each cell type and at each stage of development, large groups of genes can be regulated together. Then the expression of individual genes can be tuned by degrading a subset of the mRNAs with a single miRNA. So fewer control pathways are needed. E.g., suppose 100 genes are turned on together. A single miRNA might then turn-off ten of those genes under a specific condition. A single trans transcription factor to turn them on together with a single miRNA to turn some off would be all that is needed.

Finally, I believe you are right when you say the cost is low compared to ordinary cellular metabolism.