First it started enjoying the ‘occasional’ methylation. Then it crossed the LINE when it ‘borrowed’ its good buddy’s machinery. And now it seems like RNA just can’t stop. It turns out that just like all those hipsters, splicing isn’t the only one to enjoy an ‘alternative’ lifestyle. Researchers from UCLA have shown that polyadenylation wants to teach us a thing or two about the regulation of gene expression.
Alternative polyadenylation (APA) is a prevalent mechanism that controls gene expression by producing transcript isoforms with different poly(A) sites. Interestingly, around 30% of human genes are capable of APA and even though most of the genes with APA produce identical proteins, it has been shown to alter gene expression by changing microRNA binding sites.
Using these findings and data borrowed from the ENCODE project, researchers scanned the functional DNA elements around poly (A) cleavage sites.
Here’s what they discovered:
- Poly(A) sites are relatively insensitive to DNase1.
- Strangely, poly(A) sites had a preference for nucleosome-depleted regions, the exact opposite of what you’d expect to see with DNA that is insensitive to DNase1.
- This finding suggests that there is a role for chromatin higher order structure, rather than nucleosomes, in the reduced chromatin accessibility seen in poly(A) sites.
- When a gene uses two poly(A) sites, the more distal site shows the most chromosome accessibility, when compared to the proximal site and transcripts with only single site.
- H3K36Me3 also showed distinct patterns at the cleavage sites of genes using multiple poly(A) sites, when compared to genes with a single site.
- Interestingly, this unique signature was comparable between both sites in the case of multiple poly(A) sites but significantly different than the marks for genes with single sites.
In summary, they observed distinct patterns of DNase I sensitivity and H3K36me3 around the multiple poly (A) cleavage sites that are simultaneously used by a gene. The unique signature on these sites has the potential to serve as a marker for determining which genes use multiple poly (A) cleavage. The authors conclude that “polyadenylation and alternative polyadenylation are closely related to functional elements on the DNA level.”