Recently, SUSTech Professor Wei Chen and Professor Erin Schuman from Max-Planck-Institute for Brain Research jointly published a review titled “Circular RNAs in Brain and Other Tissues: A Functional Enigma” in Trends in Neuroscience, a top review journal in the field of neuroscience.  In this review, the authors discussed the recent advances in the detection, biogenesis and potential functions of circRNAs, with a particular focus on brain tissues.

In the last decade, genome research has fueled the discovery of an ever-growing list of novel RNA species. Beyond the classic tRNA, mRNA and rRNA, there has emerged a striking diversity of additional RNA types, including miRNA, piRNA, snoRNA, snRNA, lncRNA and other non-coding RNAs. More recently, in additional to these linear RNAs with distinct 5’ and 3’ ends, a group of circular RNAs with covalently closed loop structures has regained attention. Using RNA-seq coupled with novel bioinformatics tools, several recent studies revealed a large number of circRNAs in various cell types of organisms ranging from archea to mammals. Many of these circRNAs are abundant, stable and well-conserved during evolution. However, with few exceptions, the function of most circRNAs remains elusive.

In the last years, several studies including the one from Chen and Schuman labs demonstrated that circRNAs are much more enriched in neuronal tissues and 20% of the protein-coding genes in brain produce circRNAs.  A gene ontology analysis of the transcripts from which circRNAs are derived indicates synaptic genes are significantly enriched as circRNA host genes.  In addition, many circRNAs are enriched in synaptic fractions.  High-resolution in situ hybridization indicate the clear and unequivocal localization of circRNAs in both the cell body and dendrites of cultured hippocampal neurons and hippocampal slices (Figure below).  More importantly, circRNA expression is regulated during neuronal development and by synaptic plasticity, and often such regulation is independent of that of their host linear transcripts. All these phenomena indicate that circRNAs may hold important function in neuronal tissues. The research article jointly published by Chen and Schuman lab in Nature Neuroscience last year, titled “Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity” in 2015 has gained wide attention in the field of neuroscience.

In this review, Professor Wei Chen and Professor Erin Schuman not only reviewed the recent advance in the circRNA field, but also discussed the potential molecular mechanisms underlying the enrichment and function of circRNAs in brain tissues. Furthermore, they proposed that the long-lived nature of circRNAs as well as their localization in dendrites near synapses could allow them to bear modifications or harbor proteins or RNAs that represent the local history of the synapse.  Finally, they pointed out that high RNase resistance of circRNAs endows their high stability in blood and other body fluids, thereby makes them potential biomarkers for various diseases.   

The web link to the review article：http://dx.doi.org/10.1016/j.tins.2016.06.006