The rise of circular RNAs: a whole swath of circular Spongebobs
March 24, 2013
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Recently, we’ve been bombarded by high-profile studies about a class of RNAs, called circular RNAs. Resulting from non-canonical splicing events (see below), circRNAs seem to be more prevalent than previously thought. They’re identified in mammals, plants and even archaea.
The formation and identification of circRNAs
The recent papers in Nature (Memczak et al. and Hansem et al.) argue for a broad, even tissue specific, functionality for these type of RNAs. Memczak et al. report a comprehensive atlas of thousands of circRNAs in various organisms through a computational approach, to which they assign an impressive 75% sensitivity and very low false-discovery rate.
circRNA statistics according to Memczak et al.
The significantly high stability of these RNAs, according to these authors, puts them in perfect position to function as post-transcriptional regulators through sponging other regulatory trans factors. They focused on miRNA sites to find circRNAs that show higher than expected occurrence of these elements. Ant they in fact find circRNAs that can bind and trap miR-7 loaded RISC, results that are corroborated in other recent papers.
Personally, I find sponging a very low-complexity function… meaning, they arise after the fact, with the cell taking advantage of non-coding RNAs that are already available. This means either that circRNAs first arose as aberrant splicing events, i.e. mistakes in donor-acceptor identification or either them or their splicing partners play other, more complex roles that we should be able to identify soon.
Memczak S, et al. (2013). Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. doi:10.1038/nature11928
Hansen TB, et al. (2013). Natural RNA circles function as efficient microRNA sponges. Nature. doi:10.1038/nature11993