基于化学衍生-质谱技术的生物与临床样本中核酸修饰分析

除了经典碱基外,核酸(DNA和RNA)中还包含许多化学修饰。迄今为止,已经在核酸中鉴定了超过150多种化学修饰。这些化学修饰不会改变核酸的序列,但会改变它们的结构和生化特性,最终调节基因的时空表达。阐明这些修饰的功能可以促进对生命体生理调控机制的深入认识和理解。然而,核酸修饰在体内的丰度通常很低。因此,高灵敏和特异的检测方法对破译这些修饰的功能至关重要。化学衍生与质谱技术相结合对内源性低丰度核酸修饰展现出很好的分析能力。在过去几年中,研究者建立了多种基于化学衍生-质谱分析的分析方法,用于灵敏、高效地分析核酸修饰。该文总结了通过化学衍生-质谱分析方法来破译核酸修饰的最新进展,希望能促进未来对核酸修饰功能的深入研究。

Analysis of Nucleic Acid Modifications in Biological and Clinical Samples Based on Chemical Derivatization-Mass Spectrometry

In addition to the canonical nucleobases,nucleic acids(DNA and RNA) carry a variety of chemical modifications.More than 150 chemical modifications so far have been identified in nucleic acids.These chemical modifications do not change the sequence of nucleic acids,but may alter their structures and biochemical properties,ultimately regulating the spatiotemporal expression of genes.Uncovering the functions of these modifications could promote our understanding of the physiological regulation mechanisms of living organisms.However,the abundance of nucleic acid modifications is usually low in vivo.Therefore,highly sensitive and specific detection methods are critical to decipher the functions of nucleic acid modifications.Chemical derivatization in combination with mass spectrometry techniques demonstrate to have excellent analytical capabilities for endogenous low abundance nucleic acid modifications.In the past few years,researchers have established a variety of chemical derivatization mass spectrometry based methods for sensitive and efficient analysis of nucleic acid modifications.The recent advances in deciphering nucleic acid modifications by chemical derivatization mass spectrometry are summarized in this review,and further promotion on the future studies of nucleic acid modifications is anticipated.