Abstract
Non-coding RNAs were established in the last decade as a new valuable biomarker class for human diseases. Specifically, circular RNAs (circRNAs) were only recently discovered as a new large group of non-coding RNAs that, due to their circular configuration, are metabolically more stable compared to their linear counterparts and therefore highly suitable for biomarker use. Based on high-throughput sequencing, the catalogs of endogenous circRNAs with disease relevance and correlation continue to grow steadily. As a consequence, circRNAs emerged as novel and attractive biomarkers, indicated by numerous recent publications. Here we would like to stress the need of essential quality criteria for validation and characterization of circular RNAs. In addition to high-throughput sequencing, classical biochemical methods are essential and should be applied for the characterization of this special class of RNAs, in particular to convincingly confirm their circularity.
Highlights
Non-coding RNAs were established in the last decade as a new valuable biomarker class for human diseases
CircRNAs derived from pre-mRNAs are characterized by a covalently closed loop structure, which is generated by a special mode of alternative splicing of pre-mRNAs, called “backsplicing”: A 5′ splice site is joined to an upstream instead of a downstream 3′ splice site (Fig. 2)
CircRNA biogenesis can be promoted by cis-elements and trans-factors by bringing the corresponding splice sites in close proximity, resulting in circularization [7]
Summary
Non-coding RNAs were established in the last decade as a new valuable biomarker class for human diseases. As a relatively new class of ncRNA biomarkers, circular RNAs (circRNAs) have come more into focus within the last decade (Fig. 1). Single examples of these particular RNA species had been known for more than forty years [2], circRNAs were established as a large RNA class only a few years ago, based on high-throughput sequencing and bioinformatics [3].
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