Human ribosomal G-quadruplexes regulate heme bioavailability.
Human ribosomal G-quadruplexes regulate heme bioavailability.
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人核糖体 G-四链体调节血红素生物利用度。
DOI：
10.1074/jbc.ra120.014332
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Williams,LorenDean
中科院分区：
文献类型：
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作者：
Mestre-Fos,Santi;Ito,Chieri;Moore,CourtneyM;Reddi,AmitR;Williams,LorenDean
最近报道了人rRNA在体外形成稳定的G-四链体（G4 s）。然而，它们在细胞中的形成及其细胞作用尚未解决。在这里，通过采取化学生物学方法，整合免疫荧光，G4配体，血红素亲和试剂，和遗传编码的荧光血红素传感器的结果，我们报告说，人类核糖体可以形成G4 sin vivo调节血红素的生物利用度。免疫荧光实验表明，绝大多数核外G4与rRNA相关。此外，用G4配体滴定人类细胞改变了核糖体结合血红素的能力，并破坏了细胞血红素的生物利用度，如通过遗传编码的荧光血红素传感器所测量的。总之，这些结果表明，核糖体在调节血红素稳态中发挥作用。
Thein vitroformation of stable G-quadruplexes (G4s) in human rRNA was recently reported. However, their formation in cells and their cellular roles were not resolved. Here, by taking a chemical biology approach that integrates results from immunofluorescence, G4 ligands, heme-affinity reagents, and a genetically encoded fluorescent heme sensor, we report that human ribosomes can form G4sin vivothat regulate heme bioavailability. Immunofluorescence experiments indicate that the vast majority of extra-nuclear G4s are associated with rRNA. Moreover, titrating human cells with a G4 ligand alters the ability of ribosomes to bind heme and disrupts cellular heme bioavailability as measured by a genetically encoded fluorescent heme sensor. Overall, these results suggest that ribosomes play a role in regulating heme homeostasis.