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Related Concept Videos

Initiation of Translation02:33

Initiation of Translation

31.8K
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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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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Translation01:31

Translation

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Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
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Termination of Translation01:44

Termination of Translation

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The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
25.3K
Cotranslational Protein Translocation01:20

Cotranslational Protein Translocation

7.3K
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
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Improving Translational Accuracy02:07

Improving Translational Accuracy

9.4K
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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Related Experiment Video

Updated: Jun 14, 2025

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
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Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs

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Structural analysis of noncanonical translation initiation complexes.

Jacob M Mattingly1, Ha An Nguyen2, Bappaditya Roy3

  • 1Department of Chemistry, Emory University, Atlanta, Georgia, USA; Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University, Atlanta, Georgia, USA.

The Journal of Biological Chemistry
|September 2, 2024
PubMed
Summary

Bacterial translation initiation involves precise recognition of the initiator tRNA. Minor changes in tRNA anticodon stem interactions with the ribosome alter start codon selection, impacting protein synthesis accuracy.

Keywords:
16S rRNAA-minor motifprotein synthesistRNA(fMet)translation initiation

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • Translation initiation is a crucial, regulated step in bacterial protein synthesis.
  • The 30S ribosomal subunit, initiation factors (IFs), and initiator tRNA (fMet-tRNAfMet) assemble for initiation.
  • Accurate start codon selection relies on interactions between the ribosome, IF2, and fMet-tRNAfMet.

Purpose of the Study:

  • To investigate how modifications in fMet-tRNAfMet affect start codon recognition.
  • To elucidate the structural basis of start codon selection by the 70S ribosome.

Main Methods:

  • Electron cryomicroscopy (cryo-EM) was used to determine structures of 70S initiation complexes.
  • Structures were solved for complexes with a modified tRNA (tRNAfMet M1) and various start codons (CUG, AUG, GUG, UUG).
  • The role of initiation factor IF2 and GTP analog GDPCP was examined.

Main Results:

  • A mutation in tRNAfMet (M1) weakened A-minor interactions with 16S rRNA nucleotides A1339 and G1338.
  • Initiation factor IF2 enhanced the interaction between G1338 and the tRNA minor groove.
  • The M1 mutation reduced discrimination against the noncanonical CUG start codon.

Conclusions:

  • Slight alterations in the fMet-tRNAfMet anticodon stem recognition by the ribosome influence start codon selection.
  • Structural insights reveal how tRNA-ribosome interactions dictate translation fidelity.
  • This study highlights the intricate mechanisms governing the initiation of bacterial protein synthesis.