... finally. Sign up http://www.cellpress.com/misc/page?page=podcast> here. Or enter http://podcast.cell.com/cell.xml into your podcast subscription.
It has a nice summary of a new Hannon paper on the role of piRNA in suppression of transposons in germ cells, another summary of how WASP is anchoring actin in the lamellipodium to the membrane at the leading edge (and which fits in to the model of membrane buckling postulated in the paper that I eluded to a couple of days ago), and a paper from Gerhard Wagner's lab on a new small molecule inhibitor of eIF4E, a factor involved in the initiation of mRNA translation ... I'm actually not clear about the role of this translation factor. The Maquat lab has implicated it in the translation of mRNAs after the pioneer round of translation (I'll write about pioneer translation of mRNAs in the near future), others have implicated eIF4E in the translation of certain pool of mRNAs involved in cell division, and one group has data that indicates that eIF4E stimulates the export of this cell-cycle related mRNAs (see this post). Too bad the podcast didn't cover the tubulin-lissencephaly paper.
- Log in to post comments
Just out of curiousity, what other biology-related podcasts do you listen to? Besides Science's and Nature's, I like the Whitehead Institute's podcast.
So in the cytoplasm, eIF4E does indeed participate in translation, coupling it with eIF4A, 4G and other partners to form the eIF4F complex, which binds to the cap feature of mRNA, initiating translation. Secondly, it has been noted to be involved in the nuclear export of a subset of mRNAs involved in the cell cycle. This combines with other reports that it is involved in the translation of certain growth factors, due to increased export of these mRNAs combining with its translation properties. Both functions are seemingly separate, based on mutants available dissecting separate residues for activity, but in vivo are obviously combining.
So Wagner is claiming that the new drug, which prevents 4E from binding to 4G inhibits the translation of the subset of mRNAs that code for cell-cycle proteins. These mRNAs are "weak" and require strong strong eIF4F complex (of which 4E & 4G belong to). Why wouldn't it nuke all translation (or at least non-pioneer round translation)? I'm guess that at some level it will, but I'm surprised that there is that much of a difference.
Kirklain,
I skimmed through the paper and they claim that the drug (4EGI-1) does not affect cytosolic mRNA levels (Fig.4D), and thus they conclude that the drug is not affecting nuclear export of the mRNA. They attribute the decrease in translation to the fact that the cell-cycle mRNAs just have a greater need for eIF4F activity for translation and that the drug reduces the effective activity of eIF4F in the cell. They state that the need for eIF4F activity is determined by the 5'UTR.
Dan,
Sorry, I never answered. I use to get many podcasts and em>then never listened to any ... besides the Nature and Science I also get the NYTimes Science podacst. My wife listens to the Naked Scientist whose host (Chris Smith) also does the Nature podcast, it's good for the lay person but a bit too simple for a working scientist.
Non-science-wise, I only subscribe to This American Life's podcast, which I listen to religiously.
I'll have to give a listen to the Whitehead pocast. Any other suggestions?
The main problem with the Wagner paper, and the way he suggests that the drug is great in the podcast is that he never addresses the toxicity issue. So what if you kill cancer cells, if you attack every other cell as well. They try to answer this question with the use of transformed vs non-transformed cells, but it would have been better to go for an animal model, to show if this drug in its present state (i've heard that it needs refinement, the peptide is rather unordered even when bound) is usable or too toxic.
Wagner produces some great structures, that's not in question, but to be a cell paper? well i think he needs more, like what Rosenberg did, showing the lead compound, refinement, and mouse models: Oltersdorf et al. (2005), Nature 435, 677-681