Translation of CircRNAs.
Translation of CircRNAs.
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DOI：
10.1016/j.molcel.2017.02.021
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发表时间：
2017-04-06
期刊：
影响因子：
16
通讯作者：
Kadener S
中科院分区：
文献类型：
--
作者：
Pamudurti NR;Bartok O;Jens M;Ashwal-Fluss R;Stottmeister C;Ruhe L;Hanan M;Wyler E;Perez-Hernandez D;Ramberger E;Shenzis S;Samson M;Dittmar G;Landthaler M;Chekulaeva M;Rajewsky N;Kadener S
环状 RNA (circRNA) 是丰富且进化保守的 RNA，其功能很大程度上未知。在这里，我们展示了 circRNA 的一个子集在体内翻译。通过对果蝇头部进行核糖体足迹分析，我们证明了一组 circRNA 与核糖体翻译相关。许多核糖-circRNA 使用宿主 mRNA 的起始密码子，与膜相关核糖体结合，并具有进化上保守的终止密码子。此外，我们发现肌盲基因座产生的 circRNA 编码一种蛋白质，我们通过质谱法在果蝇头部提取物中检测到了这种蛋白质。接下来，通过进行体内和体外翻译测定，我们表明核糖-circRNA (cUTR) 的 UTR 允许帽独立翻译。此外，我们发现饥饿和 FOXO 可能调节 circMbl 同工型的翻译。总而言之，我们的研究为 circRNA 的翻译提供了强有力的证据，揭示了未探索的基因活性层的存在。特定的 circRNA 与翻译核糖体相关 核糖体足迹读取与 circMbl 的终止密码子特征相匹配 通过质谱法检测 circMbl3 衍生蛋白 circRNA 在体外和体内以不依赖于帽的方式进行翻译 Pamudurti 等人。表明 circRNA 的一个子集被翻译。这些 circRNA 通常与宿主 RNA 共享起始密码子，编码具有特定蛋白质结构域的蛋白质，并以不依赖帽子的方式进行翻译。
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. Specific circRNAs are associated with translating ribosomes Ribosome footprinting reads match termination codon signature for circMbl circMbl3-derived protein is detected by mass spectrometry circRNAs are translated in vitro and in vivo in a cap-independent manner Pamudurti et al. show that a subset of circRNAs is translated. These circRNAs generally share the start codon with the hosting RNA, encode proteins with specific protein domains, and are translated in a cap-independent manner.