Long-read Nanopore sequencing to identify isoform-specific patterns of mRNA methylation

几十年来，人们已经知道DNA和RNA分子中的组成成分或碱基可以进行化学修饰。在DNA中，这种修饰的发生和生物学功能几十年来一直是生物科学研究的一个重要领域，影响深远。与之形成鲜明对比的是，对RNA修饰的研究进展非常令人失望；这尤其令人遗憾，因为这些修饰实际上比DNA中的那些修饰更普遍，化学上也更复杂。此外，许多催化形成RNA修饰的酶与人类疾病有关，这表明了重要的生物学作用。该领域进展缓慢的一个主要原因是，事实证明，详细的研究确定RNA分子中修饰的准确位置在技术上非常困难。然而，近年来，DNA/RNA测序技术取得了重大进展，使人们能够在阐明生物功能所需的细节中识别RNA修饰。第一批此类研究是在2012年描述的，事实上，我们现在开始更充分地认识到生物科学研究中此类调查所提供的广泛范围。然而，这一研究领域仍处于早期阶段，需要实验室之间做出巨大的协调努力，才能得出这些RNA修饰的必要分子特征。这里提出的研究旨在为这方面的领域作出重大贡献。

It has for decades been known that the building blocks, or bases, within DNA and RNA molecules can be chemically modified. In DNA, the occurrence and biological function of such modifications has been a fundamentally important area of biosciences research with far-reaching impact for decades. In stark contrast, the progress of research into RNA modifications has been very disappointing; this is especially unfortunate as these modifications are actually known to be more prevalent and chemically complex than those found in DNA. Further, many of the enzymes that catalyse the formation of RNA modifications have been linked with human disease, suggesting important biological roles. A primary reason for slow progress in the field has been due to the fact that detailed studies identifying the precise positions of modifications in RNA molecules have proven technically very difficult. However in recent years, major advances in DNA/RNA sequencing techniques have been made that has allowed RNA modifications to be identified in the detail required to elucidate biological function. The first such studies were described in 2012 and indeed we are now beginning to realise more fully the broad scope offered by such investigations in biosciences research. The research field is however still in its early stages and a massive concerted effort is required between laboratories in order to yield necessary molecular characterizations of these RNA modifications. The studies proposed here aim to make major contributions to the field in this regard.