Human ribosomal G-quadruplexes regulate heme bioavailability

J Biol Chem. 2020 Oct 30;295(44):14855-14865. doi: 10.1074/jbc.RA120.014332. Epub 2020 Aug 13.

Abstract

The in vitro formation 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 G4s in vivo that 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.

Keywords: BG4; G-quadruplex; G-tract; G4; RNA; expansion segments; heme; hemin; metal homeostasis; ribosomal ribonucleic acid (rRNA) (ribosomal RNA); ribosome; tentacle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Fluorescent Antibody Technique
  • G-Quadruplexes*
  • HEK293 Cells
  • Heme / metabolism
  • Homeostasis
  • Humans
  • Ligands
  • Protein Binding
  • RNA, Ribosomal / metabolism
  • Ribosomes / metabolism*

Substances

  • Ligands
  • RNA, Ribosomal
  • Heme