生物
翻译(生物学)
RNA剪接
开放式参考框架
内部核糖体进入位点
遗传学
核糖核酸
计算生物学
RNA结合蛋白
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真核翻译
信使核糖核酸
细胞生物学
基因
肽序列
作者
Hung Ho-Xuan,Petar Glažar,Claudia Latini,Kevin Heizler,Jacob Haase,Robert Hett,Marvin Anders,Franziska Weichmann,Astrid Bruckmann,Debbie L. C. van den Berg,Stefan Hüttelmaier,Nikolaus Rajewsky,Christina Hackl,Gunter Meister
摘要
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.
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