m6A-Dependent RNA Dynamics in T Cell Differentiation
m6A-Dependent RNA Dynamics in T Cell Differentiation
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DOI：
10.3390/genes10010028
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发表时间：
2019-01-01
期刊：
影响因子：
3.5
通讯作者：
Pelizzola, Mattia
中科院分区：
文献类型：
--
作者：
Furlan, Mattia;Galeota, Eugenia;Pelizzola, Mattia
N6-甲基腺苷（m6 A）是最丰富的RNA修饰。在生理和疾病条件下，它参与调节RNA代谢，包括降解和翻译。最近的研究表明，m6 A介导的关键转录物的降解也在T细胞稳态和IL-7诱导的分化的控制中起作用。我们重新分析了该研究的组学数据，通过对总RNA-seq数据和新生RNA-seq数据的综合分析，我们能够全面量化T细胞RNA动力学以及这些如何受到m6 A耗尽的影响。除了对RNA降解的预期影响外，我们还揭示了m6 A对RNA动力学的更广泛影响，其中包括RNA合成和加工的改变。总而言之，m6 A对RNA生命周期所有主要步骤的联合作用密切地重新证明了观察到的早熟和成熟RNA种类丰度的变化。最终，我们的重新分析扩展了最初研究的结果，专注于RNA稳定性，并提出了m6 A在RNA合成和加工动力学中尚未得到重视的作用。
N6-methyladenosine (m6A) is the most abundant RNA modification. It has been involved in the regulation of RNA metabolism, including degradation and translation, in both physiological and disease conditions. A recent study showed that m6A-mediated degradation of key transcripts also plays a role in the control of T cells homeostasis and IL-7 induced differentiation. We re-analyzed the omics data from that study and, through the integrative analysis of total and nascent RNA-seq data, we were able to comprehensively quantify T cells RNA dynamics and how these are affected by m6A depletion. In addition to the expected impact on RNA degradation, we revealed a broader effect of m6A on RNA dynamics, which included the alteration of RNA synthesis and processing. Altogether, the combined action of m6A on all major steps of the RNA life-cycle closely re-capitulated the observed changes in the abundance of premature and mature RNA species. Ultimately, our re-analysis extended the findings of the initial study, focused on RNA stability, and proposed a yet unappreciated role for m6A in RNA synthesis and processing dynamics.