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Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
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Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
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Measurement of Heme Synthesis Levels in Mammalian Cells
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Human ribosomal G-quadruplexes regulate heme bioavailability.

Santi Mestre-Fos1, Chieri Ito1, Courtney M Moore2

  • 1Center for the Origin of Life, Georgia Institute of Technology, Atlanta, Georgia, USA; School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, USA; Parker Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia, USA.

The Journal of Biological Chemistry
|August 21, 2020
PubMed
Summary
This summary is machine-generated.

Human ribosomes form G-quadruplexes (G4s) in vivo, impacting heme bioavailability. This discovery reveals a novel role for G4s in regulating cellular heme homeostasis.

Keywords:
BG4G-quadruplexG-tractG4RNAexpansion segmentshemeheminmetal homeostasisribosomal ribonucleic acid (rRNA) (ribosomal RNA)ribosometentacle

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Chemical Biology

Background:

  • Stable G-quadruplexes (G4s) formation in human ribosomal RNA (rRNA) was previously shown in vitro.
  • The in vivo formation and cellular functions of these rRNA G4s remained uncharacterized.

Purpose of the Study:

  • To investigate the in vivo formation of G-quadruplexes in human ribosomes.
  • To elucidate the cellular roles of these G-quadruplexes, particularly their impact on heme bioavailability and homeostasis.

Main Methods:

  • Utilized a chemical biology approach combining immunofluorescence, G-quadruplex ligands, and heme-affinity reagents.
  • Employed a genetically encoded fluorescent heme sensor to monitor cellular heme bioavailability.
  • Investigated the association of G4s with rRNA in extra-nuclear cellular compartments.

Main Results:

  • Demonstrated that human ribosomes form G-quadruplexes in vivo.
  • Showed that the majority of extra-nuclear G4s are associated with rRNA.
  • Found that G4 ligand titration alters ribosome-heme binding and disrupts cellular heme bioavailability.

Conclusions:

  • Human ribosomes can form G-quadruplexes in vivo.
  • Ribosomal G4s play a regulatory role in heme bioavailability.
  • These findings suggest a novel mechanism for ribosome involvement in cellular heme homeostasis.