Recent advances in understanding transcription termination by RNA polymerase II.

Travis J. Loya and Daniel Reinesa,  F1000Research 2016, 5(F1000 Faculty Rev):1478  doi: 10.12688/f1000research.8455.1

R-loop-mediated termination is also proposed to play a role in Friedrich’s ataxia. It was suggested that R-loops aberrantly form in the frataxin gene as a result of expansion of GAA repeats in its first intron 58, 59. Mutated frataxin exhibits features of heterochromatin, H3K9 methylation, and decreased acetylation of H3 and H4, thus a reduced level of expression is to be expected. However, the altered gene also shares many characteristics of canonical R-loop-terminated genes, including a polyA-signal-like sequence upstream of the expansion, followed by a GU-rich sequence similar to the downstream element of polyA signals. This has led to a proposal that the mutated frataxin allele is the victim of premature termination, which contributes to its low level of expression in patients. While experimental verification is still needed, this is an interesting model for a role of termination in disease.