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Circ-MALAT1 Functions as Both an mRNA Translation Brake and a microRNA Sponge to Promote Self-Renewal of Hepatocellular Cancer Stem Cells.
Advanced Science ( IF 14.3 ) Pub Date : 2019-12-21 , DOI: 10.1002/advs.201900949
Liang Chen 1, 2 , Ruijiao Kong 3 , Cong Wu 1 , Shuo Wang 1 , Zixin Liu 1 , Shupeng Liu 1 , Shuiping Li 4 , Tian Chen 1 , Chuanbin Mao 5 , Shanrong Liu 3
Affiliation  

Both circular RNAs (circRNAs) and cancer stem cells (CSCs) are separately known to be involved in cancer, but their interaction remains unclear. Here, the regulation of hepatocellular CSC self-renewal is discovered by a circRNA, circ-MALAT1, which is produced by back-splicing of a long noncoding RNA, MALAT1. Circ-MALAT1 is highly expressed in CSCs from clinical hepatocellular carcinoma samples under the mediation of an RNA-binding protein, AUF1. Surprisingly, circMALAT1 functions as a brake in ribosomes to retard PAX5 mRNA translation and promote CSCs' self-renewal by forming an unprecedented ternary complex with both ribosomes and mRNA. The discovered braking mechanism of a circRNA, termed mRNA braking, along with its more traditional role of miRNA sponging, uncovers a dual-faceted pattern of circRNA-mediated post-transcriptional regulation for maintaining a specific cell state.

中文翻译:


Circ-MALAT1 既充当 mRNA 翻译刹车又充当 microRNA 海绵,促进肝细胞癌干细胞的自我更新。



已知环状 RNA (circRNA) 和癌症干细胞 (CSC) 均与癌症有关,但它们的相互作用仍不清楚。在这里,肝细胞 CSC 自我更新的调节是由 circRNA(circ-MALAT1)发现的,它是由长非编码 RNA(MALAT1)反向剪接产生的。在 RNA 结合蛋白 AUF1 的介导下,Circ-MALAT1 在临床肝细胞癌样本的 CSC 中高表达。令人惊讶的是,circMALAT1 作为核糖体中的制动器,通过与核糖体和 mRNA 形成前所未有的三元复合物来延迟 PAX5 mRNA 翻译并促进 CSC 的自我更新。所发现的 circRNA 制动机制(称为 mRNA 制动)及其更传统的 miRNA 海绵作用,揭示了 circRNA 介导的转录后调节维持特定细胞状态的双重模式。
更新日期:2019-12-21
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