Comprehensive analysis of translation from overexpressed circular RNAs reveals pervasive translation from linear transcripts

被引：59

作者：

Hung Ho-Xuan ^{[1
]}

Glazar, Petar ^{[2
]}

Latini, Claudia ^{[1
]}

Heizler, Kevin ^{[1
]}

Haase, Jacob ^{[3
]}

Hett, Robert ^{[1
]}

Anders, Marvin ^{[4
]}

Weichmann, Franziska ^{[1
]}

Bruckmann, Astrid ^{[1
]}

Van den Berg, Debbie ^{[5
]}

Huttelmaier, Stefan ^{[3
]}

Rajewsky, Nikolaus ^{[2
]}

Hackl, Christina ^{[4
]}

Meister, Gunter ^{[1
]}

机构：

[1] Univ Regensburg, Regensburg Ctr Biochem RCB, Lab RNA Biol, Regensburg, Germany

[2] Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Lab Syst Biol Gene Regulatory Elements, Berlin, Germany

[3] Martin Luther Univ Halle Wittenberg, Charles Tanford Prot Ctr, Sect Mol Cell Biol, Inst Mol Med, D-06120 Halle, Germany

[4] Univ Hosp Regensburg, Dept Surg, Regensburg, Germany

[5] Erasmus MC, Dept Cell Biol, Wytemaweg 80, NL-3015 CN Rotterdam, Netherlands

来源：

NUCLEIC ACIDS RESEARCH | 2020年 / 48卷 / 18期

基金：

欧洲研究理事会;

关键词：

BIOGENESIS; CIRCRNAS; ABUNDANT; REPEATS; EXON;

D O I：

10.1093/nar/gkaa704

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：10368 / 10382

页数：15