Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università di Milano, Segrate 20054, Italy.
Earth-Life Science Institute, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan.
Nucleic Acids Res. 2024 Nov 11;52(20):12689-12700. doi: 10.1093/nar/gkae823.
The ribosome, owing to its exceptional conservation, harbours a remarkable molecular fossil known as the protoribosome. It surrounds the peptidyl transferase center (PTC), responsible for peptide bond formation. While previous studies have demonstrated the PTC activity in RNA alone, our investigation reveals the intricate roles of the ribosomal protein fragments (rPeptides) within the ribosomal core. This research highlights the significance of rPeptides in stability and coacervation of two distinct protoribosomal evolutionary stages. The 617nt 'big' protoribosome model, which associates with rPeptides specifically, exhibits a structurally defined and rigid nature, further stabilized by the peptides. In contrast, the 136nt 'small' model, previously linked to peptidyltransferase activity, displays greater structural flexibility. While this construct interacts with rPeptides with lower specificity, they induce coacervation of the 'small' protoribosome across a wide concentration range, which is concomitantly dependent on the RNA sequence and structure. Moreover, these conditions protect RNA from degradation. This phenomenon suggests a significant evolutionary advantage in the RNA-protein interaction at the early stages of ribosome evolution. The distinct properties of the two protoribosomal stages suggest that rPeptides initially provided compartmentalization and prevented RNA degradation, preceding the emergence of specific RNA-protein interactions crucial for the ribosomal structural integrity.
核糖体由于其特殊的保守性,蕴藏着一种被称为原核核糖体的显著分子化石。它围绕着肽基转移酶中心(PTC),负责肽键的形成。虽然之前的研究已经证明了 RNA 单独具有 PTC 活性,但我们的研究揭示了核糖体蛋白片段(rPeptides)在核糖体核心中的复杂作用。这项研究强调了 rPeptides 在两个不同原核核糖体进化阶段的稳定性和凝聚中的重要性。与 rPeptides 特异性结合的 617nt“大”原核核糖体模型表现出结构定义和刚性的性质,进一步由肽稳定。相比之下,以前与肽基转移酶活性相关的 136nt“小”模型显示出更大的结构灵活性。虽然这种构建体与 rPeptides 的特异性较低,但它们在广泛的浓度范围内诱导“小”原核核糖体的凝聚,这与 RNA 序列和结构同时相关。此外,这些条件还能保护 RNA 免受降解。这种现象表明,在核糖体进化的早期阶段,RNA-蛋白质相互作用具有重要的进化优势。两个原核核糖体阶段的不同性质表明,rPeptides 最初提供了隔室化作用并防止了 RNA 降解,随后出现了对于核糖体结构完整性至关重要的特定 RNA-蛋白质相互作用。