Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA; Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP 01246, Brazil.
Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Semin Cancer Biol. 2021 Nov;76:292-300. doi: 10.1016/j.semcancer.2021.08.012. Epub 2021 Aug 30.
Post-transcriptional (PtscM) and post-translational (PtrnM) modifications of nucleotides and amino acids are covalent modifications able to change physio-chemical properties of RNAs and proteins. In the ribosome, the adequate assembly of rRNAs and ribosomal protein subunits in the nucleolus ensures suitable translational activity, with protein synthesis tuned according to intracellular demands of energy production, replication, proliferation, and growth. Disruption in the regulatory control of PtscM and PtrnM can impair ribosome biogenesis and ribosome function. Ribosomal impairment may, in turn, impact the synthesis of proteins engaged in functions as varied as telomere maintenance, apoptosis, and DNA repair, as well as intersect with mitochondria and telomerase activity. These cellular processes often malfunction in carcinogenesis and senescence. Here we discuss regulatory mechanisms of PtscMs and PtrnMs on ribosomal function. We also address chemical modification in rRNAs and their impacts on cellular metabolism, replication control, and senescence. Further, we highlight similarities and differences of PtscMs and PtrnMs in ribosomal intermediates during aging and carcinogenesis. Understanding these regulatory mechanisms may uncover critical steps for the development of more efficient oncologic and anti-aging therapies.
核苷酸和氨基酸的转录后(PtscM)和翻译后(PtrnM)修饰是能够改变 RNA 和蛋白质理化性质的共价修饰。在核糖体中,rRNA 和核糖体蛋白亚基在核仁中的适当组装确保了适当的翻译活性,根据细胞内能量产生、复制、增殖和生长的需求来调节蛋白质合成。PtscM 和 PtrnM 的调节控制的破坏会损害核糖体的生物发生和核糖体的功能。核糖体的损伤反过来又会影响参与端粒维持、细胞凋亡和 DNA 修复等各种功能的蛋白质的合成,并与线粒体和端粒酶活性相互交叉。这些细胞过程在癌变和衰老过程中经常出现故障。在这里,我们讨论 PtscM 和 PtrnM 对核糖体功能的调节机制。我们还讨论了 rRNA 中的化学修饰及其对细胞代谢、复制控制和衰老的影响。此外,我们强调了衰老和癌变过程中核糖体中间产物中 PtscM 和 PtrnM 的相似性和差异。了解这些调节机制可能揭示出开发更有效肿瘤学和抗衰老疗法的关键步骤。