Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377, München, Germany.
Nat Commun. 2021 Dec 8;12(1):7123. doi: 10.1038/s41467-021-27371-9.
Queuosine (Q) is a structurally complex, non-canonical RNA nucleoside. It is present in many eukaryotic and bacterial species, where it is part of the anticodon loop of certain tRNAs. In higher vertebrates, including humans, two further modified queuosine-derivatives exist - galactosyl- (galQ) and mannosyl-queuosine (manQ). The function of these low abundant hypermodified RNA nucleosides remains unknown. While the structure of galQ was elucidated and confirmed by total synthesis, the reported structure of manQ still awaits confirmation. By combining total synthesis and LC-MS-co-injection experiments, together with a metabolic feeding study of labelled hexoses, we show here that the natural compound manQ isolated from mouse liver deviates from the literature-reported structure. Our data show that manQ features an α-allyl connectivity of its sugar moiety. The yet unidentified glycosylases that attach galactose and mannose to the Q-base therefore have a maximally different constitutional connectivity preference. Knowing the correct structure of manQ will now pave the way towards further elucidation of its biological function.
Queuosine (Q) 是一种结构复杂的非典型 RNA 核苷。它存在于许多真核生物和细菌物种中，是某些 tRNA 反密码环的一部分。在包括人类在内的高等脊椎动物中，还存在两种进一步修饰的 queuosine 衍生物——半乳糖基（galQ）和甘露糖基-queuosine (manQ)。这些低丰度的高度修饰 RNA 核苷的功能仍然未知。虽然 galQ 的结构已经通过全合成得到阐明和证实，但报道的 manQ 结构仍有待证实。通过全合成和 LC-MS 共注射实验，以及对标记己糖的代谢喂养研究，我们在这里表明，从鼠肝中分离出的天然化合物 manQ 偏离了文献报道的结构。我们的数据表明，manQ 的糖部分具有α-烯丙基连接性。因此，将半乳糖和甘露糖连接到 Q 碱基上的尚未鉴定的糖苷酶具有最大不同的结构连接偏好。了解 manQ 的正确结构将为进一步阐明其生物学功能铺平道路。
