Translation is required for miRNA-dependent decay of endogenous transcripts
Translation is required for miRNA-dependent decay of endogenous transcripts
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内源转录本的 miRNA 依赖性衰减需要翻译
DOI：
10.1101/2020.01.21.913483
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
A. C. Marques
中科院分区：
文献类型：
--
作者：
Adriano Biasini;Stefano de Pretis;J. Tan;Baroj Abdulkarim;Harry Wischnewski;R. Dreos;Mattia Pelizzola;C. Ciaudo;A. C. Marques
microRNA（miRNA）的转录后抑制通过转录不稳定或翻译抑制发生。尽管RNA降解解释了大多数miRNA依赖性抑制，但转录物降解同时发生，这引起了关于靶翻译对miRNA依赖性转录物不稳定的要求的问题。为了评估翻译对miRNA介导的RNA不稳定的贡献，我们通过解剖miRNA功能丧失对胞质长非编码RNA（lncRNA）的影响来解耦这两个分子过程。我们发现，尽管与miRNA加载的RNA诱导沉默复合物（miRISC）相互作用，这些内源性表达的非翻译转录物的稳态丰度和降解速率受miRNA丢失的影响最小。为了验证miRNA依赖性衰变的翻译要求，我们将miRISC结合的lncRNA（其水平不受miRNA影响）融合到蛋白质编码基因报告基因的3 '末端，并表明这导致其miRNA依赖性转录物不稳定。此外，对水平受miRNA调控的少数lncRNA的分析显示，这些lncRNA倾向于与翻译核糖体相关，并且可能是错误注释的微肽，进一步证实了靶翻译对miRNA依赖性转录物衰变的必要性。我们的分析揭示了翻译对miRNA依赖性转录物不稳定的严格要求，并证明编码和非编码转录物的水平受到miRNA的不同影响。
Posttranscriptional repression by microRNA (miRNA) occurs through transcript destabilization or translation inhibition. Whereas RNA degradation explains most miRNA-dependent repression, transcript decay occurs co-translationally, raising questions regarding the requirement of target translation to miRNA-dependent transcript destabilization. To assess the contribution of translation to miRNA-mediated RNA destabilization, we decoupled these two molecular processes by dissecting the impact of miRNA loss of function on cytosolic long noncoding RNAs (lncRNAs). We show, that despite interacting with miRNA loaded RNA-induced silencing complex (miRISC), the steady state abundance and degradation rates of these endogenously expressed non-translated transcripts are minimally impacted by miRNA loss. To validate the requirement of translation for miRNA-dependent decay, we fused a miRISC bound lncRNA, whose levels are unaffected by miRNAs, to the 3’end of a protein-coding gene reporter and show that this results in its miRNA-dependent transcript destabilization. Furthermore, analysis of the few lncRNAs whose levels are regulated by miRNAs revealed these tend to associate with translating ribosomes and are likely misannotated micropeptides, further substantiating the necessity of target translation for miRNA-dependent transcript decay. Our analyses reveal the strict requirement of translation for miRNA-dependent transcript destabilization and demonstrate that the levels of coding and noncoding transcripts are differently affected by miRNAs.
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