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Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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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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ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Is there a localized role for translational quality control?

Sezen Meydan1,2, Nicholas R Guydosh3

  • 1National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

RNA (New York, N.Y.)
|August 15, 2023
PubMed
Summary

Cellular gene expression is localized, but mechanisms remain unclear. This review explores how ribosome quality control (QC) pathways may regulate localized translation and gene expression, offering future research directions.

Keywords:
ISRNMDRQCdisomeribosome

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • mRNA and translation machinery are not uniformly distributed in the cytoplasm.
  • Localized gene expression enables cellular functions like growth and signaling in 3D space.
  • The precise functions and mechanisms of localized gene expression are not fully understood.

Purpose of the Study:

  • To explore the role of ribosome quality control (QC) mechanisms in localized gene expression.
  • To review existing studies on QC pathways and their involvement in localized translation.
  • To propose future research directions for understanding QC's role in localized gene expression.

Main Methods:

  • Review of existing literature on cellular QC pathways.
  • Analysis of studies investigating QC pathways in localized translation.
  • Identification of knowledge gaps and formulation of research questions.

Main Results:

  • QC pathways globally detect and resolve aberrant translation events.
  • The impact of QC pathways on local translation remains largely unknown.
  • Some QC pathways are enriched near specific organelles, suggesting potential localized activity.

Conclusions:

  • QC pathways are critical for maintaining translational fidelity.
  • Further research is needed to determine how QC pathways influence localized gene expression.
  • Understanding QC's role could reveal new mechanisms for controlling cellular spatial organization and function.