Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis

By Ivano Legnini, Gaia Di Timoteo, F. Rossi, M. Morlando, Francesca Briganti, O. Sthandier, Alessandro Fatica, Tiziana Santini, A. Andronache, M. Wade and 3 more. Molecules and Cells, 2017

1,878 citations recorded by the source corpus.

Summary Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and still largely unknown functions. Their biogenesis, which proceeds via a back-splicing reaction, is fairly well characterized, whereas their role in the modulation of physiologically relevant processes is still unclear. Here we performed expression profiling of circRNAs during in vitro differentiation of murine and human myoblasts, and we identified conserved species regulated in myogenesis and altered in Duchenne muscular dystrophy. A high-content functional genomic screen allowed the study of their functional role in muscle differentiation. One of them, circ-ZNF609, resulted in specifically controlling myoblast proliferation. Circ-ZNF609 contains an open reading frame spanning from the start codon, in common with the linear transcript, and terminating at an in-frame STOP codon, created upon circularization. Circ-ZNF609 is associated with heavy polysomes, and it is translated into a protein in a splicing-dependent and cap-independent manner, providing an example of a protein-coding circRNA in eukaryotes.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a4207963c3b8d8a7de4eec16cf8a808d0e0e80a6

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Citations in the corpus

• Past, present, and future of circRNAs (2019, neutral): “Its N-terminal DNA-binding domain might be expressed from the circRNA (Legnini et al , 2017) and might compete for the DNA-binding sites with the full-length Mef2 or even have a function on its own (He et al , 2011; Legnini et al , 2017).”
• CircRNA: functions and properties of a novel potential biomarker for cancer (2017, background): “found that circ-ZNF609 could translate proteins in murine myoblasts when driven by IRES (internal ribosome entry site) [30].”
• Circular RNA-protein interactions: functions, mechanisms, and identification (2020, background): “There are several well-studied protein-coding circRNAs: circ-ZNF609 [100], circ-FBXW7 [38], circSHPRH [101], cirPINTexon2 [102], circMbl [103], and the recently reported circ-AKT3 [104] (Table 3).”
• Circbank: a comprehensive database for circRNA with standard nomenclature (2019, background): “For example, the human circZNF609 was found to be translated into protein and play a role in controlling myoblast proliferation [25].”
• Circular RNAs: Promising Biomarkers for Human Diseases (2018, background): “It has been confirmed that circ-ZNF609 can be translated into protein functioning in myogenesis [27].”
• The bioinformatics toolbox for circRNA discovery and analysis (2020, background): “2017, endogenous circRNA was shown to be translated into functional polypeptides [16, 166, 175].”
• Circular RNA: metabolism, functions and interactions with proteins (2020, background): “For example, m6A improves the efficiency of IRES-mediated translation of circZNF609 [39, 83].”
• Circular RNA and its mechanisms in disease: From the bench to the clinic. (2018, background): “010 into a protein through a splicing-dependent, cap-independent mechanism (Legnini et al., 2017), providing thefirst indication that endogenous circRNAs can in fact encode proteins.”