Pervasive translation of circular RNAs driven by short IRES-like elements.
Pervasive translation of circular RNAs driven by short IRES-like elements.
复制标题
由类似 IRES 的短元件驱动的环状 RNA 的普遍翻译
DOI：
10.1038/s41467-022-31327-y
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发表时间：
2022-06-29
影响因子：
16.6
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Fan X;Yang Y;Chen C;Wang Z
一些环状RNA（circRNA）被发现是通过IRES驱动机制进行翻译的，但由于内源性IRES很少见，所以circRNA翻译的范围和功能尚不清楚。为了确定 circRNA 翻译的普遍性和机制，我们开发了一个基于细胞的系统来筛选随机序列并识别 97 个过度代表性的六聚体，这些六聚体驱动帽独立的 circRNA 翻译。这些类似 IRES 的短元件在内源性 circRNA 中显着富集，足以驱动 circRNA 翻译。我们进一步鉴定了多个结合这些 IRES 样元件以启动翻译的反式作用因子。使用质谱数据，鉴定了数百种 circRNA 编码的肽，其中大多数由于快速降解而丰度较低。根据质谱分析判断，50% 的可翻译内源性 circRNA 经历了滚环翻译，其中一些经过了实验验证。一致的是，一种 circRNA 中 IRES 样元件的突变会减少其翻译。总的来说，我们的研究结果表明 circRNA 的翻译是普遍存在的，这为翻译控制提供了深远的影响。对随机序列的无偏筛选发现了许多短的IRES样元件来驱动环状RNA翻译和数百个滚环翻译事件，这表明人类转录组中普遍存在不依赖帽的翻译。
Some circular RNAs (circRNAs) were found to be translated through IRES-driven mechanism, however the scope and functions of circRNA translation are unclear because endogenous IRESs are rare. To determine the prevalence and mechanism of circRNA translation, we develop a cell-based system to screen random sequences and identify 97 overrepresented hexamers that drive cap-independent circRNA translation. These IRES-like short elements are significantly enriched in endogenous circRNAs and sufficient to drive circRNA translation. We further identify multiple trans-acting factors that bind these IRES-like elements to initiate translation. Using mass-spectrometry data, hundreds of circRNA-coded peptides are identified, most of which have low abundance due to rapid degradation. As judged by mass-spectrometry, 50% of translatable endogenous circRNAs undergo rolling circle translation, several of which are experimentally validated. Consistently, mutations of the IRES-like element in one circRNA reduce its translation. Collectively, our findings suggest a pervasive translation of circRNAs, providing profound implications in translation control. Unbiased screen of random sequences identified many short IRES-like elements to drive circular RNA translation and hundreds of rolling circle translation events, suggesting a pervasive cap-independent translation in human transcriptome.
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影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
全面鉴定环状RNA的内部结构和选择性剪接事件
影响因子：
16.6
作者：
Gao Y;Wang J;Zheng Y;Zhang J;Chen S;Zhao F
通讯作者：
Zhao F
DOI：
10.1002/wrna.1465
发表时间：
2018-05
期刊：
Wiley interdisciplinary reviews. RNA
影响因子：
--
作者：
Harvey RF;Smith TS;Mulroney T;Queiroz RML;Pizzinga M;Dezi V;Villenueva E;Ramakrishna M;Lilley KS;Willis AE
通讯作者：
Willis AE
影响因子：
4.6
作者：
Abe N;Matsumoto K;Nishihara M;Nakano Y;Shibata A;Maruyama H;Shuto S;Matsuda A;Yoshida M;Ito Y;Abe H
通讯作者：
Abe H
影响因子：
4.6
作者：
Barrett, Steven P.;Salzman, Julia
通讯作者：
Salzman, Julia