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Translational Regulation01:29

Translational Regulation

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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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Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
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Analysis of Global RNA Synthesis at the Single Cell Level following Hypoxia
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Hypoxia re-programs 2'-O-Me modifications on ribosomal RNA.

Brandon J Metge1, Sarah C Kammerud1, Hawley C Pruitt1

  • 1Department of Pathology, University of Alabama at Birmingham, WTI 320E 1824 6 Avenue South, Birmingham, AL 35233, USA.

Iscience
|January 25, 2021
PubMed
Summary

Hypoxia alters ribosome methylation patterns, leading to specialized ribosomes that enhance translation of key tumor progression genes like VEGF. This ribosomal heterogeneity impacts cellular function under stress.

Keywords:
Molecular BiologyMolecular Mechanism of Gene RegulationProteomics

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Area of Science:

  • Cellular biology
  • Molecular oncology
  • Biochemistry

Background:

  • Hypoxia is a critical cellular stressor in conditions like cancer.
  • Hypoxia influences gene translation via internal ribosome entry site (IRES) mechanisms.
  • Vascular Endothelial Growth Factor (VEGF) is crucial for tumor growth and is regulated by IRES-mediated translation.

Purpose of the Study:

  • To investigate the impact of hypoxia on RNA Polymerase I activity and ribosomal RNA (rRNA) methylation.
  • To explore the role of ribosomal heterogeneity in cellular responses to hypoxia.
  • To determine if differentially methylated ribosomes in hypoxia affect IRES-mediated translation of specific genes.

Main Methods:

  • Analysis of RNA Polymerase I activity under hypoxic conditions.
  • Assessment of rRNA methylation patterns in hypoxia versus normoxia.
  • Investigation of ribosome composition and heterogeneity.
  • Functional assays to examine VEGF-C IRES recognition by specific ribosome subsets.

Main Results:

  • Hypoxia significantly upregulates RNA Polymerase I activity.
  • Distinct rRNA methylation patterns are observed in hypoxia compared to normoxia.
  • Evidence suggests the generation of functionally specialized ribosomes under hypoxic stress.
  • A subset of these differentially methylated ribosomes specifically recognizes the VEGF-C IRES.

Conclusions:

  • Hypoxia induces significant changes in rRNA methylation, creating ribosomal heterogeneity.
  • This ribosomal heterogeneity enables altered translational control in response to hypoxic stress.
  • Specialized ribosomes in hypoxia can preferentially translate specific IRES-containing mRNAs like VEGF-C, impacting tumor progression.