Circadian control of mRNA polyadenylation dynamics regulates rhythmic protein expression
Circadian control of mRNA polyadenylation dynamics regulates rhythmic protein expression
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DOI：
10.1101/gad.208306.112
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发表时间：
2012-12-15
影响因子：
10.5
通讯作者：
Green, Carla B.
中科院分区：
文献类型：
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作者：
Kojima, Shihoko;Sher-Chen, Elaine L.;Green, Carla B.
Poly(A) tails是真核生物mRNA的3'修饰，在翻译和mRNA稳定性的控制中起重要作用。我们鉴定了数百种小鼠肝脏mrna，它们在poly(A)尾巴的长度上表现出强大的昼夜节律。其中大约80%主要是核腺苷化与节律性转录结合的结果。然而，独特的衰变动力学将这些mrna与其他mrna区分开来，这些mrna有节奏地转录，但不表现出多(A)尾节律。剩余的20%与转录解偶联，即使稳态mRNA水平没有节律性，也表现出多(A)尾节律。这些是在有节奏的细胞质聚腺苷化的控制下，至少在某些情况下由细胞质聚腺苷化元件结合蛋白（CPEBs）调节。重要的是，我们发现poly(A)尾巴长度的节律性与蛋白质表达的节律性密切相关，尾巴最长的时间与蛋白质水平最高的时间之间有几个小时的延迟。我们的研究表明，生物钟调节mrna的动态聚腺苷化状态，这可能导致有节奏的蛋白质表达独立于稳态水平的信息。
Poly(A) tails are 3' modifications of eukaryotic mRNAs that are important in the control of translation and mRNA stability. We identified hundreds of mouse liver mRNAs that exhibit robust circadian rhythms in the length of their poly(A) tails. Approximately 80% of these are primarily the result of nuclear adenylation coupled with rhythmic transcription. However, unique decay kinetics distinguish these mRNAs from other mRNAs that are transcribed rhythmically but do not exhibit poly(A) tail rhythms. The remaining 20% are uncoupled from transcription and exhibit poly(A) tail rhythms even though the steady-state mRNA levels are not rhythmic. These are under the control of rhythmic cytoplasmic polyadenylation, regulated at least in some cases by cytoplasmic polyadenylation element-binding proteins (CPEBs). Importantly, we found that the rhythmicity in poly(A) tail length is closely correlated with rhythmic protein expression, with a several-hour delay between the time of longest tail and the time of highest protein level. Our study demonstrates that the circadian clock regulates the dynamic polyadenylation status of mRNAs, which can result in rhythmic protein expression independent of the steady-state levels of the message.