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Related Concept Videos

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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Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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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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Leaky Scanning02:28

Leaky Scanning

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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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Regulated mRNA Transport02:22

Regulated mRNA Transport

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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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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.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
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Initiation of Translation02:33

Initiation of Translation

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Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
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In Vitro Transcribed RNA-based Luciferase Reporter Assay to Study Translation Regulation in Poxvirus-infected Cells
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Selective translational control of cellular and viral mRNAs by RPS3 mRNA binding.

Tal Havkin-Solomon1, Elad Itzhaki1, Nir Joffe1

  • 1Dept. of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot 7610001, Israel.

Nucleic Acids Research
|April 18, 2023
PubMed
Summary

Ribosomal protein RPS3

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Area of Science:

  • Molecular Biology
  • Genetics
  • Virology

Background:

  • RPS3 is a core component of the 40S ribosomal subunit, interacting with mRNA.
  • Its role in specific mRNA translation and ribosome specialization in mammals is unclear.

Purpose of the Study:

  • To investigate the impact of RPS3 mRNA-binding residues on cellular and viral translation.
  • To explore RPS3's role in SARS-CoV-2 translation and host-pathogen interactions.

Main Methods:

  • Site-directed mutagenesis of RPS3 mRNA-contacting residues (R116, R146, K148).
  • Translatome analysis to identify differentially translated genes.
  • Investigation of RPS3 interactions with SARS-CoV-2 components.

Main Results:

  • Mutations in RPS3 residues differentially affected translation initiation, scanning, and start-codon fidelity.
  • RPS3 influences translation of genes with specific 5'UTR features.
  • RPS3 mRNA-binding is crucial for SARS-CoV-2 NSP1-mediated translation inhibition and viral mRNA stability.

Conclusions:

  • RPS3 mRNA-binding residues possess diverse translation regulatory functions.
  • SARS-CoV-2 exploits RPS3's mRNA-binding for its own translational advantage and stability.
  • RPS3 plays a significant role in both host and viral mRNA regulation.