Dipartimento di Bioscienze, Università degli Studi di Milano, via Celoria 26, 20133 Milano, Italy.
Int J Mol Sci. 2020 Mar 2;21(5):1706. doi: 10.3390/ijms21051706.
In the last decade, it has become evident that RNA is frequently found in DNA. It is now well established that single embedded ribonucleoside monophosphates (rNMPs) are primarily introduced by DNA polymerases and that longer stretches of RNA can anneal to DNA, generating RNA:DNA hybrids. Among them, the most studied are R-loops, peculiar three-stranded nucleic acid structures formed upon the re-hybridization of a transcript to its template DNA. In addition, polyribonucleotide chains are synthesized to allow DNA replication priming, double-strand breaks repair, and may as well result from the direct incorporation of consecutive rNMPs by DNA polymerases. The bright side of RNA into DNA is that it contributes to regulating different physiological functions. The dark side, however, is that persistent RNA compromises genome integrity and genome stability. For these reasons, the characterization of all these structures has been under growing investigation. In this review, we discussed the origin of single and multiple ribonucleotides in the genome and in the DNA of organelles, focusing on situations where the aberrant processing of RNA:DNA hybrids may result in multiple rNMPs embedded in DNA. We concluded by providing an overview of the currently available strategies to study the presence of single and multiple ribonucleotides in DNA in vivo.
在过去的十年中,人们已经明显认识到 RNA 经常存在于 DNA 中。现在已经确定,单嵌入核糖核苷单磷酸酯(rNMP)主要由 DNA 聚合酶引入,并且较长的 RNA 链可以与 DNA 退火,形成 RNA:DNA 杂交体。其中,研究最多的是 R 环,这是一种特殊的三链核酸结构,是转录本与其模板 DNA 重新杂交时形成的。此外,多聚核苷酸链被合成以允许 DNA 复制引发、双链断裂修复,并且可能是由于 DNA 聚合酶直接连续掺入连续的 rNMP 所致。RNA 掺入 DNA 的好处是它有助于调节不同的生理功能。然而,不利的一面是,持续存在的 RNA 会损害基因组的完整性和稳定性。出于这些原因,对所有这些结构的特性的研究一直在不断深入。在这篇综述中,我们讨论了基因组和细胞器 DNA 中单核苷酸和多个核苷酸的起源,重点讨论了 RNA:DNA 杂交体异常加工可能导致多个 rNMP 嵌入 DNA 的情况。最后,我们概述了目前可用于研究体内 DNA 中单核苷酸和多个核苷酸存在的策略。