tag:blogger.com,1999:blog-14815894.post2222602471542214118..comments2024-03-29T03:15:36.192-04:00Comments on Bayblab: mRNA structures translationally prefered by cancerKamelhttp://www.blogger.com/profile/15548259062576527751noreply@blogger.comBlogger5125tag:blogger.com,1999:blog-14815894.post-3543325731074920552009-04-03T19:46:00.000-04:002009-04-03T19:46:00.000-04:00microRNA transcripts are specifically less transla...<I>microRNA transcripts are specifically less translationally upregulated in the eIF4E overexpressors.</I><BR/><BR/>That makes sense.<BR/><BR/>Question is, do tumor cells have other ways of over-stimulating translation that are miRNA insensitive? I suspect so.<BR/><BR/>But at the least this data definitely supports the idea that miRNA-mediated translational repression is via a 4E/cap-dependent related mechanism. That's interesting.<BR/><BR/>Are picornaviral IRES-driven transcripts insensitive to miRNA-mediated translational repression?Baymanhttps://www.blogger.com/profile/03436172198266062229noreply@blogger.comtag:blogger.com,1999:blog-14815894.post-90388972273612423072009-04-03T16:51:00.000-04:002009-04-03T16:51:00.000-04:00I don't know all the evidence but I think that eIF...I don't know all the evidence but I think that eIF4E is supposed to be a reasonable model for the different types of translational dysregulation that occurs in cancer. AKT signalling, ect.<BR/>Also I interpret their results as saying that microRNA transcripts are specifically less translationally upregulated in the eIF4E overexpressors. Not that the overexpressors have less expression of microRNA regulated transcripts, just less upregulated.<BR/>I agree with your last paragraph, I think. If translation initiation is no longer rate limiting it is likely something else is. I don't know if that effects any of their interpretation but it's interesting. Elongation might actually make sense if you look at the repeating pattern in the ORF in the GC content data. But apparently that was already known.Robhttps://www.blogger.com/profile/11878582460269426199noreply@blogger.comtag:blogger.com,1999:blog-14815894.post-37802225855918845852009-04-02T14:19:00.000-04:002009-04-02T14:19:00.000-04:00Or.. this form of translational dysregulation is n...<I>Or.. this form of translational dysregulation is not able to overcome the microRNA mediated translational repression.</I><BR/><BR/>Yeah I think that makes sense and that seems to be more the argument presented in the paper. (now that that I read it). But the thing is that the "form of translational dysregulation" they are talking about is artificial overexpression of eIF4E. I find it confusing to think about what this means in real life.<BR/><BR/>I think what they're trying to say, as you alluded to, is that 4E dependent translation is uniquely sensitive to miRNA regulation. But compared to what? In these experiments, compared to un-molested cells. But isn't almost all translation 4E (cap) dependent, even in unmolested cells? This is where I get confused.<BR/><BR/>Maybe when 4E is overexpressed, some other aspect of translation becomes rate limiting, other than cap-recognition. For example, elongation. So they're picking up signatures of mRNAs that are well translated when elongation, or whatever step X, is limiting, when cap-binding proteins are in excess.Baymanhttps://www.blogger.com/profile/03436172198266062229noreply@blogger.comtag:blogger.com,1999:blog-14815894.post-20376264692584536702009-04-02T12:56:00.000-04:002009-04-02T12:56:00.000-04:00I have to say that I doubt this study is picking o...<I>I have to say that I doubt this study is picking of mRNAs that are preferred by cancer cells. Rather, it is picking up signatures of difficult to translate mRNAs (ie secondary structure, GC content) which are relatively much more abundant in polysomes when the translational machinery becomes hyperactivated and therefore less picky about substrates.</I><BR/>I think there is evidence that indeed cancer cells are just less picky about substrates and therefore preferentially translate these messages which are enriched in messages for tumourgenesis and tumour progression.<BR/><I>Also the fact that cancer cells show a "preference" for miRT-free mRNAs is bizarre. The only explanation I can think of is that miRNAs are generally overexpressed in cancer.</I><BR/>Or.. this form of translational dysregulation is not able to overcome the microRNA mediated translational repression.Robhttps://www.blogger.com/profile/11878582460269426199noreply@blogger.comtag:blogger.com,1999:blog-14815894.post-62972649958636317282009-04-02T10:49:00.000-04:002009-04-02T10:49:00.000-04:00I like the idea.I have to say that I doubt this st...I like the idea.<BR/><BR/>I have to say that I doubt this study is picking of mRNAs that are preferred by cancer cells. Rather, it is picking up signatures of difficult to translate mRNAs (ie secondary structure, GC content) which are relatively much more abundant in polysomes when the translational machinery becomes hyperactivated and therefore less picky about substrates.<BR/><BR/>Also the fact that cancer cells show a "preference" for miRT-free mRNAs is bizarre. The only explanation I can think of is that miRNAs are generally overexpressed in cancer.Baymanhttps://www.blogger.com/profile/03436172198266062229noreply@blogger.com