It’s almost time to hit the road, for a trip to Seattle for the RNA 2010 Meeting. I’m not one for blogging meetings or stuff like that, but I can provide a bit of a taste for what will be happening.
Two recent reports from the Pubmed wires:
One report describes a global analysis of 3′-UTRs in C. elegans. This group collected information on 3′-UTRs at different stages of development of the organism; this information came from data mining, cDNA and 3′-RACE sequencing, and 454 sequencing of 3′-end tags (to briefly summarize the approaches – read the paper to get a better flavor). There is lots of information in the paper, but two things revisit issues that have been discussed in this blog. One matter is that there is extensive alternative polyadenylation, such that mRNAs early in development are shorter longer than those later in development. This is because of extensive alternative polyadenylation, and the result is recalls findings from similar studies in humans. It would seem as if, in animals at least, there is a global and important shift in poly(A) site choice during development. The mechanism(s) underlying this shift remain an open question.
Second, there is no canonical poly(A) signal for many of the alternative polyadenylation sites that these authors see. This is also similar to what is seen in humans, and recalls the more general themes of poly(A) signals that are discussed in this essay. While no specifics can be stated, this suggests that the polyadenylation apparatus early in development is different, or that it is modified or regulated such that it has a different set of RNA sequence preferences. It will be fascinating to see how these questions sort out.
A second report describes an interesting genetic screen that implicates a C. elegans homolog of the yeast polyadenylation factor subunit PFS2 in neural development. (Sorry for the link to Pubmed – the journal doesn’t yet have the link up. Also, obviously, I am going by the abstract here. If the paper raises additional issues, I will update this essay appropriately.) This is interesting because the plant homolog of Pfs2, FY, has important regulatory functions in flowering and in chromatin-mediated gene silencing. This raises the interesting (but highly speculative) possibility of an evolutionarily-conserved function for FY/PFS2. It will be interesting to see if the C. elegans homolog plays analogous roles in chromatin modification.
A recent study of transgene expression in plants revisits themes that recur in the literature every so often. Namely, that “alternative polyadenylation” and low-level transcription well beyond a plant polyadenylation signal are common occurrences in plants. These phenomena are not limited to just transgenes, but are seen with most (if not all) genes.
Why the scare quotes? Because, while the events documented in this study are formally occurrences of alternative polyadenylation, they reflect the inherent 3′ end microheterogeneity that is seen in almost all plant genes, and probably involves subtly different handling of a single polyadenylation signal. This sort of poly(A) site heterogeneity should be distinguished from the occurrence of clearly distinct polyadenylation signals, separated by hundreds or thousands of nucleotides along a transcript.
In any case, this short report reinforces the notion that transcriptional readthrough from transgenes can impact the expression of “host” genes via posttranscriptional gene silencing.