Molecular, Cellular and Developmental Biology Unit (MCD), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, 31062, Toulouse, France.
Genomic Stability and Biotherapy (GSBT) Laboratory, Faculty of Sciences, Rafik Hariri Campus, Lebanese University, Beirut, Lebanon.
Nat Commun. 2021 Oct 22;12(1):6153. doi: 10.1038/s41467-021-26207-w.
Synthesis of eukaryotic ribosomes involves the assembly and maturation of precursor particles (pre-ribosomal particles) containing ribosomal RNA (rRNA) precursors, ribosomal proteins (RPs) and a plethora of assembly factors (AFs). Formation of the earliest precursors of the 60S ribosomal subunit (pre-60S r-particle) is among the least understood stages of ribosome biogenesis. It involves the Npa1 complex, a protein module suggested to play a key role in the early structuring of the pre-rRNA. Npa1 displays genetic interactions with the DExD-box protein Dbp7 and interacts physically with the snR190 box C/D snoRNA. We show here that snR190 functions as a snoRNA chaperone, which likely cooperates with the Npa1 complex to initiate compaction of the pre-rRNA in early pre-60S r-particles. We further show that Dbp7 regulates the dynamic base-pairing between snR190 and the pre-rRNA within the earliest pre-60S r-particles, thereby participating in structuring the peptidyl transferase center (PTC) of the large ribosomal subunit.
真核核糖体的合成涉及到含有核糖体 RNA (rRNA) 前体、核糖体蛋白 (RPs) 和大量组装因子 (AFs) 的前体颗粒 (pre-ribosomal particles) 的组装和成熟。60S 核糖体亚基 (pre-60S r-particle) 的最早前体的形成是核糖体生物发生中了解最少的阶段之一。它涉及 Npa1 复合物,该蛋白模块被认为在 pre-rRNA 的早期结构中发挥关键作用。Npa1 与 DExD-box 蛋白 Dbp7 存在遗传相互作用,并与 snR190 框 C/D snoRNA 相互作用。我们在这里表明,snR190 作为 snoRNA 伴侣发挥作用,可能与 Npa1 复合物合作,启动早期 pre-60S r-particle 中 pre-rRNA 的压缩。我们进一步表明,Dbp7 调节 snR190 和 pre-rRNA 之间在最早的 pre-60S r-particle 内的动态碱基配对,从而参与大亚基肽转移酶中心 (PTC) 的结构形成。