Exon circularization requires canonical splice signals.

By S. Starke, Isabelle Jost, O. Rossbach, Tim Schneider, S. Schreiner, Lee‐Hsueh Hung, A. Bindereif. Cell Reports, 2015

719 citations recorded by the source corpus.

Circular RNAs (circRNAs), an abundant class of noncoding RNAs in higher eukaryotes, are generated from pre-mRNAs by circularization of adjacent exons. Using a set of 15 circRNAs, we demonstrated their cell-type-specific expression and circular versus linear processing in mammalian cells. Northern blot analysis combined with RNase H cleavage conclusively proved a circular configuration for two examples, LPAR1 and HIPK3. To address the circularization mechanism, we analyzed the sequence requirements using minigenes derived from natural circRNAs. Both canonical splice sites are required for circularization, although they vary in flexibility and potential use of cryptic sites. Surprisingly, we found that no specific circRNA exon sequence is necessary and that potential flanking intron structures can modulate circularization efficiency. In combination with splice inhibitor assays, our results argue that the canonical spliceosomal machinery functions in circRNA biogenesis, constituting an alternative splicing mode.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9cb07b6d45eb184e1e06612cd13ab4a12c5d0507

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In Molecular Biology

Citations in the corpus

Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis (2017, background): “We found that the backsplicing formed the 620 nt circ-FBXW7 instead of the 1227 nt circ-FBXW7 as reported in Circbase (hsa_circ_0001451), most likely due to intronic sequence shearing (29).”
Identification and Characterization of Circular RNAs As a New Class of Putative Biomarkers in Human Blood (2015, background): “Most circRNAs are probably products of a ‘back-splice’ reaction that joins a splice donor site with an upstream splice acceptor site [4,5].”
CSCD: a database for cancer-specific circular RNAs (2017, background): “Inhibition of canonical spliceosome by mRNA splicing inhibitor reduces both the levels of circRNA and the parent linear transcript, indicating the role of mRNA spliceosome in circRNA biogenesis (17).”
Diverse alternative back-splicing and alternative splicing landscape of circular RNAs (2016, positive): “…spliceosomal machinery (Ashwal-Fluss et al. 2014; Starke et al. 2015; Wang and Wang 2015) and modulated by both cis -elements and trans -factors (Ashwal-Fluss et al. 2014; Zhang et al. 2014; Conn et al. 2015; Ivanov et al. 2015; Starke et al. 2015; for review, see Chen and Yang 2015; Chen 2016).”
Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis (2017, background): “Publi This is an open access article under the CC BY-NC-ND license (http:// 2014; Starke et al., 2015; Conn et al., 2015).”
Circular RNAs: analysis, expression and potential functions (2016, background): “Thus, the function (Li et al., 2015; Memczak et al., 2013) and biogenesis (Ashwal-Fluss et al., 2014; Barrett et al., 2015; Kramer et al., 2015; Liang and Wilusz, 2014; Starke et al., 2015) of circRNAs is often studied using easily manipulable circRNA overexpression plasmids.”
Circular RNA: metabolism, functions and interactions with proteins (2020, background): “CircRNA biogenesis relies on canonical splicing machinery, including splice signal sites and spliceosomes [31].”
Circular RNA-protein interactions: functions, mechanisms, and identification (2020, background): “CircRNAs are transcribed by RNA Pol II and are generated by the spliceosome, which includes heterogeneous nuclear ribonucleoproteins (hnRNPs) such as the small ribonucleoprotein particle U1 subunits 70K and C (snRNP-U1-70K and snRNP-U1-C, respectively), and the SR proteins [60].”
Regulation of circRNA biogenesis (2015, background): “Nevertheless, it has been shown that both canonical splice signals and canonical spliceosomal machinery are required for back-spliced circularization.(29,30) In addition, the majority of highly expressed circRNAs are usually processed from internal exons of pre-mRNAs and normally contain multiple ex”