Alex Palazzo is an Assistant Professor in the Department of Biochemistry at The University of Toronto.
Here I am, in the lab with one last experiment to go before I leave to feast on a Christmas Eve dinner, so while I wait for that last centrifugation step, I'll write a quick post about all these great papers on RNA Polymerase II and chromatin remodelling. As I've said before, if you want to understand what is going on with all of these non-coding RNA transcripts, you have to understand how DNA is organized.
If you don't understand how DNA is packed in the typical eukaryotic (i.e. nucleated) cell, please read this:
How Transcription Affects Genomic Organization and Vice Versa
Then to get you up to speed on the latest findings, read this:
Activating a gene through pioneer transcripts
Now, on to the new stuff.
Since I'm pressed for time I'll just point out a few manuscripts that appeared in the past month that indicate how widespread transcription throughout the genome affects the packing of DNA which ultimately affects the expression of protein-coding genes.
Bottom line: upstream transcription affects histone modifications that help to regulate the Gal gene promoter.
Bottom line: when you deplete the nuclear exosome (the main RNA degradation machine in the eukaryotic nucleus), all of these "upstream" transcripts appear, both sense and anti-sense. The authors speculate that this has something to do with gene activation.
Bottom line: The authors report that almost half of all genes produce anti-sense transcripts. From the paper:
The distribution of antisense transcripts was distinct from that of sense transcripts, was nonrandom across the genome, and differed among cell types.
Bottom line: again the depletion of that same exosome complex results in the appearance of ncRNAs. But the authors also find that the exosome component Rrp6 also genetically interacts with mRNA export factors!
And hot off the press:
I haven't had the time to fully digest what's in this paper, but here's the abstract:
In addition to RNA polymerases I, II, and III, the essential RNA polymerases present in all eukaryotes, plants have two additional nuclear RNA polymerases, abbreviated as Pol IV and Pol V, that play nonredundant roles in siRNA-directed DNA methylation and gene silencing. We show that Arabidopsis Pol IV and Pol V are composed of subunits that are paralogous or identical to the 12 subunits of Pol II. Four subunits of Pol IV are distinct from their Pol II paralogs, six subunits of Pol V are distinct from their Pol II paralogs, and four subunits differ between Pol IV and Pol V. Importantly, the subunit differences occur in key positions relative to the template entry and RNA exit paths. Our findings support the hypothesis that Pol IV and Pol V are Pol II-like enzymes that evolved specialized roles in the production of noncoding transcripts for RNA silencing and genome defense.
SO TO SUMMARIZE ...
It's looking more and more like the act of transcribing RNA deeply affects how DNA is packed especially with respect to histone modification. In many ways, this cross talk between RNA polymerase and chromatin organization, has been known for a while, but it is becoming increasingly clear that this activity is occurring throughout the entire genome.
Now the questions become
1) how does the RNA degradation machinery "know" which transcript is the nc-RNA byproduct of this cross-talk and thus a substrate for degradation
2) how do the splicing and RNA nuclear export machineries "know" which transcripts are the real thing! We have pretty good evidence that these filters work very well in eukaryotes and there is a lot of genetic evidence that the RNA degredation machinery and the histone modification machinery communicate somehow to the proteins involved in mRNA nuclear export. This RNA filtering process is one of the main differences between euks and proks. But that filter is looking more and more mysterious.
Life Science
Comments
Great piece on the incredibly complexity of transcription. Also really enjoyed the background links.
brainhealthhacks.com
Posted by: Ward | December 26, 2008 11:09 AM
"1) how does the RNA degradation machinery "know" which transcript is the nc-RNA byproduct of this cross-talk and thus a substrate for degradation"?
To add related thought - might the Arabidopsis polIV and polV -derived transcripts be less susceptible to exosome-mediated degradation in the nucleus? Nominally, these enzymes seem to produce primarily nc-like RNAs, but these RNAs must be abundant enough to function in silencing.
It's fun to think about, to be sure.
"2) how do the splicing and RNA nuclear export machineries "know" which transcripts are the real thing"?
Indeed.
Posted by: Arthur Hunt | December 28, 2008 1:39 AM
Wow! Thanks. A great compilation. I appreciate how you gave the bottom-line for each one.
Posted by: suganthi | December 29, 2008 12:36 PM
Thanks for the update. I am always interested in RNA degradation :0
Posted by: Marguerite McDonald | December 30, 2008 10:51 AM