The Role of Circular RNAs in Molecular Biology of the Brain

Our research focuses on studying brain transcriptome using next-generation sequencing, in particular, RNA-Seq technique. We are interested in region-specific gene expression profiles in brain development and ageing as well as perturbation of the transcriptome as a result of neurodegeneration.

Recent advances in genomic technology allowed to uncover new RNA species, circular RNAs (circRNAs; Fig. 1). CircRNAs have been identified as a naturally occurring family of widespread and diverse endogenous noncoding RNAs that may regulate gene expression in mammals (Huang et al. 2017) and are perturbed as a result of neurodegeneration (Chen et al. 2016). They are unusually stable RNA molecules with cell type- or developmental stage-specific expression patterns. However, the role of circRNAs in molecular biology of the brain remains unknown. Hence, the aim of this project is to investigate changes in circRNA expression signatures in mouse and human neocortex. The second research aim is to discover new mechanisms of inteaction between linear and circular transcripts specifically expressed in the brain. The project will involve RNA-Seq data analysis combined with experimental validation of identified circRNA candidates.

Canonical splicing (left panel) leads to generation of linear mRNAs whereas
backsplicing (right panel), involving the joining of a downstream 5’ splice site of an
exon to an upstream 3’ splice site of another exon, results in circRNAs lacking free 5’ and 3’ ends
(Huang et al. 2017).


References

  • Chen BJ, Ueberham U, Mills JD, Kirazov L, Kirazov E, Knobloch M, Bochmann J, Jendrek R, Takenaka K, Bliim N, Arendt T & Janitz M, 2017, ‘RNA sequencing reveals pronounced changes in the noncoding transcriptome of aging synaptosomes’, Neurobiol Aging, 56:67-77.
  • Chen BJ, Mills JD, Takenaka K, Bliim N, Halliday GM & Janitz M, 2016, ‘Characterization of circular RNAs landscape in multiple system atrophy brain’, J Neurochem, 139:485-496.
  • Huang S, Yang B, Chen BJ, Bliim N, Ueberham U, Arendt T & Janitz M, 2017, ‘The emerging role of circular RNAs in transcriptome regulation’, Genomics, pii: S0888-7543(17)30046-0.

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