Human tissue-specific circular RNA signatures

Our research focuses on studying circular transcriptome in the human brain and peripheral tissues using RNA sequencing. We are particularly interested in the role of circular RNAs (circRNAs) in regulation of molecular physiology of human tissues. Moreover, we aim to identify circRNAs which can serve as biomarkers of early onset of human complex diseases.

Fig. 1. Canonical splicing (left panel) leads to generation of linear mRNAs whereas backsplicing (right panel), involving the joining of a upstream 5’ splice site of an exon to an downstream 3’ splice site of another exon, results in circRNAs lacking free 5’ and 3’ ends (Huang et al. 2017). 

Recent advances in genomic technology allowed discovery of a 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) and cancer (Chen et al. 2017). They are unusually stable RNA molecules with cell type- or developmental stage-specific expression patterns. However, the role of circRNAs in molecular biology within the human tissues remains unknown. Hence, the aim of this project is to investigate circRNA expression signatures in 11 healthy, human tissues including adipose, colon, heart, hypothalamus, kidney, liver, lung, ovary, skeletal muscle, spleen and testes. The second research aim is to discover new mechanisms of interaction between linear and circular transcripts specifically expressed in individual tissues. The project will involve RNA-Seq data analysis combined with experimental validation of identified circRNA candidates.

References

Chen BJ, Byrne FL, Takenaka K, Modesitt SC, Olzomer EM, Mills JD, Farrell R, Hoehn KL & Janitz M (2017) Analysis of the circular RNA transcriptome in endometrial cancer. Oncotarget, 9:5786-5796.

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, 109:401-407.



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