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Related Concept Videos

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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Improving Translational Accuracy02:07

Improving Translational Accuracy

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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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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

22.9K
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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Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
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Quantitative Immunofluorescence to Measure Global Localized Translation
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Cap-Independent Circular mRNA Translation Efficiency.

Andrei A Deviatkin1,2, Ruslan A Simonov1,3, Kseniya A Trutneva1,2

  • 1Life Sciences Research Center, Moscow Institute of Physics and Technology, National Research University, 141700 Dolgoprudniy, Russia.

Vaccines
|February 28, 2023
PubMed
Summary

Circular messenger RNA (mRNA) vaccines offer enhanced stability over traditional mRNA vaccines by eliminating vulnerable ends. This review explores cap-independent translation initiation for developing novel circular mRNA vaccines and biotechnological products.

Keywords:
cap-independent translationcircRNAmRNA vaccines

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Area of Science:

  • Biotechnology
  • Vaccinology
  • Molecular Biology

Background:

  • Messenger RNA (mRNA) vaccines are pivotal in infectious disease control.
  • Conventional mRNA vaccines face instability issues due to exoribonucleases, necessitating specialized storage and limiting accessibility.
  • The five-prime and three-prime ends of linear mRNA are susceptible to degradation, impacting vaccine efficacy and shelf-life.

Purpose of the Study:

  • To review current knowledge on cap-independent translation initiation methods for circular mRNAs.
  • To discuss the potential of circular mRNA technology in developing more stable and accessible vaccines.
  • To explore applications of circular mRNAs in biotechnology beyond vaccines.

Main Methods:

  • Literature review of existing research on mRNA stability and translation.
  • Analysis of cap-independent translation initiation mechanisms.
  • Comparative assessment of linear versus circular mRNA platforms for vaccine development.

Main Results:

  • Circular mRNAs lack the vulnerable 5' and 3' ends, conferring inherent stability.
  • Canonical translation initiation is not possible with circular mRNAs due to the absence of a 5' cap.
  • Various cap-independent translation initiation strategies exist and are being investigated.

Conclusions:

  • Circular mRNA technology presents a promising avenue for overcoming the stability limitations of current mRNA vaccines.
  • Further research into cap-independent translation is crucial for realizing the full potential of circular mRNA vaccines.
  • Circular mRNAs could revolutionize vaccine development and other biotechnological applications by improving stability and accessibility.