Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
Trends Biochem Sci. 2024 Jan;49(1):12-27. doi: 10.1016/j.tibs.2023.10.008. Epub 2023 Dec 14.
The uridine modifications pseudouridine (Ψ), dihydrouridine, and 5-methyluridine are present in eukaryotic mRNAs. Many uridine-modifying enzymes are associated with human disease, underscoring the importance of uncovering the functions of uridine modifications in mRNAs. These modified uridines have chemical properties distinct from those of canonical uridines, which impact RNA structure and RNA-protein interactions. Ψ, the most abundant of these uridine modifications, is present across (pre-)mRNAs. Recent work has shown that many Ψs are present at intermediate to high stoichiometries that are likely conducive to function and at locations that are poised to influence pre-/mRNA processing. Technological innovations and mechanistic investigations are unveiling the functions of uridine modifications in pre-mRNA splicing, translation, and mRNA stability, which are discussed in this review.
尿嘧啶修饰核苷假尿嘧啶(Ψ)、二氢尿嘧啶和 5-甲基尿嘧啶存在于真核生物的 mRNA 中。许多尿嘧啶修饰酶与人类疾病相关,这突显了揭示 mRNA 中尿嘧啶修饰功能的重要性。这些修饰的尿嘧啶具有与典型尿嘧啶不同的化学性质,影响 RNA 结构和 RNA-蛋白质相互作用。在这些尿嘧啶修饰中,最为丰富的是 Ψ,它存在于(前)mRNA 中。最近的研究表明,许多 Ψ 以可能有利于功能的中等至高化学计量存在,并位于可能影响前/mRNA 加工的位置。技术创新和机制研究正在揭示尿嘧啶修饰在 pre-mRNA 剪接、翻译和 mRNA 稳定性中的功能,本文对此进行了讨论。