Distinguishing RNA modifications from noise in epitranscriptome maps

Distinguishing RNA modifications from noise in epitranscriptome maps
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DOI:
10.1038/nchembio.2546
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发表时间:
2018-03-01
影响因子:
14.8
通讯作者:
Jaffrey, Samie R.
Jaffrey, Samie R.
中科院分区:
生物学1区
文献类型:
--
作者:
Grozhik, Anya V.;Jaffrey, Samie R.

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信使RNA(MRNA)和长非编码RNA(LncRNA)可以受到各种转录后修饰,这些修饰显著影响它们的命运和功能。这种“表位转录”修饰的概念和对其功能的理解一直受到使用下一代测序技术绘制修饰核苷酸的转录组范围的新技术的推动。测绘技术已经成功地记录了转录组中几个修饰核苷酸的位置和流行情况。然而,一些作图方法已经导致了普遍存在的新的RNA修饰的提议,随后被证明是异常罕见的。这些争议导致了对组成mRNA和lncRNA表位转录组的修饰核苷酸的同一性的混淆。在这里,我们讨论了不同的转录组技术来定位修饰的核苷酸。我们描述了为什么这些方法的准确性和特异性很差。最后,我们描述了将假阳性和其他与作图和测量表位转录修饰相关的陷阱降至最低的新兴策略。
Messenger RNA (mRNA) and long noncoding RNA (lncRNA) can be subjected to a variety of post-transcriptional modifications that markedly influence their fate and function. This concept of 'epitranscriptomic' modifications and the understanding of their function has been driven by new technologies for transcriptome-wide mapping of modified nucleotides using next-generation sequencing. Mapping technologies have successfully documented the location and prevalence of several modified nucleotides in the transcriptome. However, some mapping methods have led to proposals of pervasive novel RNA modifications that have subsequently been shown to be exceptionally rare. These controversies have resulted in confusion about the identity of the modified nucleotides comprising the epitranscriptome in mRNA and lncRNA. Here we discuss the different transcriptome-wide technologies for mapping modified nucleotides. We describe why these methods can have poor accuracy and specificity. Finally, we describe emerging strategies that minimize false positives and other pitfalls associated with mapping and measuring epitranscriptomic modifications.