Hung, Ho-Xuan and Glazar, Petar and Latini, Claudia and Heizler, Kevin and Haase, Jacob and Hett, Robert and Anders, Marvin and Weichmann, Franziska and Bruckmann, Astrid and Van den Berg, Debbie and Huttelmaier, Stefan and Rajewsky, Nikolaus and Hackl, Christina and Meister, Gunter (2020) Comprehensive analysis of translation from overexpressed circular RNAs reveals pervasive translation from linear transcripts. NUCLEIC ACIDS RESEARCH, 48 (18). pp. 10368-10382. ISSN 0305-1048, 1362-4962
Full text not available from this repository. (Request a copy)Abstract
Circular RNAs (circRNAs) encompass a widespread and conserved class of RNAs, which are generated by back-splicing of downstream 5' to upstream 3' splice sites. CircRNAs are tissue-specific and have been implicated in diseases including cancer. They can function as sponges for microRNAs (miRNAs) or RNA binding proteins (RBPs), for example. Moreover, some contain open reading frames (ORFs) and might be translated. The functional relevance of such peptides, however, remains largely elusive. Here, we report that the ORF of circZNF609 is efficiently translated when expressed from a circZNF609 overexpression construct. However, endogenous proteins could not be detected. Moreover, initiation of circZNF609 translation is independent of m6A-generating enzyme METTL3 or RNA sequence elements such as internal ribosome entry sites (IRESs). Surprisingly, a comprehensive mutational analysis revealed that deletion constructs, which are deficient in producing circZNF609, still generate the observed protein products. This suggests that the apparent circZNF609 translation originates from trans-splicing by-products of the overexpression plasmids and underline that circRNA overexpression constructs need to be evaluated carefully, particularly when functional studies are performed.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BIOGENESIS; CIRCRNAS; ABUNDANT; REPEATS; EXON; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Mar 2021 06:49 |
| Last Modified: | 09 Mar 2021 06:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43576 |
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