Pamudurti Nagarjuna Reddy, Bartok Osnat, Jens Marvin, Ashwal-Fluss Reut, Stottmeister Christin, Ruhe Larissa, Hanan Mor, Wyler Emanuel, Perez-Hernandez Daniel, Ramberger Evelyn, Shenzis Shlomo, Samson Moshe, Dittmar Gunnar, Landthaler Markus, Chekulaeva Marina, Rajewsky Nikolaus, Kadener Sebastian
Biological Chemistry Department, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Systems Biology of Gene Regulatory Elements, Max-Delbrück-Center for Molecular Medicine, Berlin 13125, Germany.
Mol Cell. 2017 Apr 6;66(1):9-21.e7. doi: 10.1016/j.molcel.2017.02.021. Epub 2017 Mar 23.
Circular RNAs (circRNAs) are abundant and evolutionarily conserved RNAs of largely unknown function. Here, we show that a subset of circRNAs is translated in vivo. By performing ribosome footprinting from fly heads, we demonstrate that a group of circRNAs is associated with translating ribosomes. Many of these ribo-circRNAs use the start codon of the hosting mRNA, are bound by membrane-associated ribosomes, and have evolutionarily conserved termination codons. In addition, we found that a circRNA generated from the muscleblind locus encodes a protein, which we detected in fly head extracts by mass spectrometry. Next, by performing in vivo and in vitro translation assays, we show that UTRs of ribo-circRNAs (cUTRs) allow cap-independent translation. Moreover, we found that starvation and FOXO likely regulate the translation of a circMbl isoform. Altogether, our study provides strong evidence for translation of circRNAs, revealing the existence of an unexplored layer of gene activity.
环状RNA（circRNAs）是一类丰富且在进化上保守的RNA，其功能大多未知。在此，我们表明一部分circRNAs在体内被翻译。通过对果蝇头部进行核糖体足迹分析，我们证明一组circRNAs与正在翻译的核糖体相关联。这些核糖体结合的circRNAs中有许多使用宿主mRNA的起始密码子，被膜相关核糖体结合，并且具有进化上保守的终止密码子。此外，我们发现由肌肉盲基因座产生的一种circRNA编码一种蛋白质，我们通过质谱在果蝇头部提取物中检测到了该蛋白质。接下来，通过进行体内和体外翻译实验，我们表明核糖体结合的circRNAs（cUTRs）的非翻译区允许不依赖帽结构的翻译。此外，我们发现饥饿和FOXO可能调节circMbl异构体的翻译。总之，我们的研究为circRNAs的翻译提供了有力证据，揭示了基因活性中一个未被探索的层面的存在。
