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Comment
. 2017 Dec 12:10:412.
doi: 10.3389/fnmol.2017.00412. eCollection 2017.

Commentary: FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons

Bert M Verheijen  1 , R Jeroen Pasterkamp  1
Affiliations
Comment

Commentary: FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons

Bert M Verheijen et al. Front Mol Neurosci. .
No abstract available

Keywords: FUS; RNA-binding protein; circular RNA; motor neuron disease; splicing.

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Figures

Figure 1
Figure 1
Circular RNAs and motor neuron disease. (A) Circular RNAs (circRNAs) are generated in a “non-canonical” splicing event (Sibley et al., 2016), referred to as “back-splicing.” In back-splicing reactions, a downstream 5′ splice site (splice donor) is joined to an upstream 3′ splice site (splice acceptor) to form a covalently closed loop structure. A horizontal line indicates the head-to-tail junction of the circRNA. circRNAs have biochemical properties that distinguish them from linear RNA species. For example, they are highly resistant to exonucleases, because they lack free 5′ and 3′ ends. Treatment of RNA with the magnesium-dependent 3′->5′exoribonuclease RNAse R efficiently digests linear RNA, but not circRNA (Suzuki et al., ; Chu et al., 2017). (B) In recent years, it has become clear that circRNAs are widely expressed in cells and that some may have specific biological functions. This has resulted in profound interest in circRNAs as supported by an increasing number of publications listed in PubMed. (C) circRNAs have been shown to be deregulated in motor neuron disease (1) and might carry out specific roles in motor neurons. Potential functions of circRNAs include the regulation of transcription and pre-mRNA splicing (2). A study in Arabidopsis has shown that a circRNA can interact with its cognate DNA locus via complementary base-pairing to produce a DNA-RNA hybrid, or R-loop, to promote alternative splicing of its corresponding mRNA, altering floral morphology (Conn et al., 2017). Aberrant circRNA-DNA interactions may be partly responsible for neuronal abnormalities, e.g., elevated levels of R-loops have been found in motor neuron disease models (e.g., Walker et al., 2017). Additionally, circRNAs are involved in circRNA-protein (circRNP) complex formation and localization, sponging of other RNAs (e.g., miRNAs) and RNA-binding proteins (RBPs), and may be translated into proteins/peptides (3). circRNAs may control oscillations in transcriptional networks (e.g., as molecular components of the circadian clock) and influence processes like pluripotency maintenance and neuronal differentiation (You et al., ; Yu et al., 2017). In addition, circRNAs might play roles in the formation of aggregates and stress granules (4) and can also be secreted, perhaps acting as trans-acting signaling molecules (5).
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