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解析细胞命运决定和发育中的表观转录组特征。

Deciphering the Epitranscriptomic Signatures in Cell Fate Determination and Development.

机构信息

National Centre for Cell Science, S. P. Pune University Campus, Ganeshkhind, Pune, 411007, India.

出版信息

Stem Cell Rev Rep. 2019 Aug;15(4):474-496. doi: 10.1007/s12015-019-09894-3.

Abstract

Precise regulation of transcriptome modulates several vital aspects in an organism that includes gene expression, cellular activities and development, and its perturbation ensuing pathological conditions. Around 150 post-transcriptional modifications of RNA have been identified till date, which are evolutionarily conserved and likewise prevalent across RNA classes including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and detected less frequently in small nuclear RNA (snRNA) and microRNAs (miRNA). Among the RNA modifications documented, N6-methyladenosine (mA) is the best characterised till date. Also, N-methyladenosine (mA), 5-methylcytosine (mC) and pseudouridine (Ψ) are some of the other prominent modifications detected in coding and non-coding RNAs. "Epitranscriptome", ensemble of these post-transcriptional RNA modifications, precisely coordinates gene expression and biological processes. Current literatures suggest the critical involvement of epitranscriptomics in several organisms during early development, contributing to cell fate specification and physiology. Indeed, epitranscriptomics similar to DNA epigenetics involves combinatorial dynamics provided by modified RNA molecules and associated protein complexes, which function as "writers", "erasers" and "readers" of these modifications. A novel code orchestrating gene expression during cell fate determination is generated by the coordinated effects of different classes of modified RNAs and its regulator proteins. In this review, we summarize the current knowhow on N6-methyladenosine (mA), 5-methylcytosine (mC) and pseudouridine (ψ) modifications in RNA, the associated regulator proteins and enumerate how the epitranscriptomic regulations are involved in cell fate determination.

摘要

精确调节转录组可调节生物体的多个重要方面,包括基因表达、细胞活动和发育,以及由此导致的病理状况。迄今为止,已经鉴定出大约 150 种 RNA 的转录后修饰,这些修饰在进化上是保守的,同样存在于信使 RNA(mRNA)、转移 RNA(tRNA)、核糖体 RNA(rRNA)等 RNA 类别中,在小核 RNA(snRNA)和 microRNA(miRNA)中检测到的频率较低。在已记录的 RNA 修饰中,N6-甲基腺苷(mA)是迄今为止研究最充分的一种。此外,N6-甲基腺苷(mA)、5-甲基胞嘧啶(mC)和假尿嘧啶(Ψ)是在编码和非编码 RNA 中检测到的其他一些主要修饰。“转录后组学”,即这些转录后 RNA 修饰的集合,精确协调基因表达和生物过程。目前的文献表明,在早期发育过程中,转录后组学在几种生物体中都有重要的参与,有助于细胞命运的特化和生理功能。实际上,与 DNA 表观遗传学类似,转录后组学涉及由修饰 RNA 分子及其相关蛋白复合物提供的组合动力学,它们充当这些修饰的“写入器”、“擦除器”和“读取器”。通过不同类别修饰 RNA 和其调节蛋白的协调作用,在细胞命运决定过程中生成了一种新的基因表达调控码。在这篇综述中,我们总结了 RNA 中 N6-甲基腺苷(mA)、5-甲基胞嘧啶(mC)和假尿嘧啶(Ψ)修饰、相关调节蛋白的最新知识,并列举了转录后组学调控如何参与细胞命运决定。

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