In Pnueli et al., 2015, they knock down an enhancer RNA using RNAi, testing whether it is a mere byproduct or whether it has a key role in the enhancer's function. They find their system works: the siRNA knocks down the enhancer RNA that it's targeted to, enabling further study. Hooray!
... but I've read that RNAi and the RISC work outside the nucleus, and intra-nuclear effects are further downstream and indirect (example: Gosline et al. assume that effects on introns are indirect). I assume the paper's not wrong, so what's going on?
- Conventional wisdom is wrong or incomplete: RNAi can work inside the nucleus too.
- Pneuli et al.'s enhancer RNA gets exported to the cytoplasm and then re-imported to act on its target gene.
- Something else?
Pnueli, L., Rudnizky, S., Yosefzon, Y., & Melamed, P. (2015). RNA transcribed from a distal enhancer is required for activating the chromatin at the promoter of the gonadotropin α-subunit gene. Proceedings of the National Academy of Sciences, 112(14), 4369-4374.
Gosline, S. J., Gurtan, A. M., JnBaptiste, C. K., Bosson, A., Milani, P., Dalin, S., ... & Fraenkel, E. (2016). Elucidating microRNA regulatory networks using transcriptional, post-transcriptional, and histone modification measurements. Cell reports, 14(2), 310-319.