Related Experiment Video
Updated: May 29, 2026
09:52
An In Vitro Single-Molecule Imaging Assay for the Analysis of Cap-Dependent Translation Kinetics
Published on: September 15, 2020
Molecular mechanism of scanning and start codon selection in eukaryotes
1Laboratory of Gene Regulation and Development, Eunice K. Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. alanh@mail.nih.gov
Microbiology and Molecular Biology Reviews : MMBR
|September 3, 2011
Summary
Ribosomal scanning accurately initiates mRNA translation by scanning the 40S subunit along mRNA. This process, involving initiation factors and RNA helicases, ensures correct AUG codon recognition for protein synthesis.
Area of Science:
- Molecular Biology
- Genetics
- Structural Biology
Background:
- mRNA translation initiation is crucial for protein synthesis.
- The scanning mechanism is the primary pathway for eukaryotic mRNA translation initiation.
- Accurate AUG codon recognition is essential for initiating translation at the correct site.
Purpose of the Study:
- To elucidate the molecular mechanism of ribosomal scanning during mRNA translation initiation.
- To understand the roles of initiation factors and RNA helicases in this process.
Main Methods:
- Yeast genetics
- Biochemical analysis in reconstituted systems
- Structural biology
Main Results:
- A molecular model for ribosomal scanning has been developed.
- Eukaryotic initiation factor 1 (eIF1) and eIF1A stabilize an open 40S subunit conformation for scanning.
- DEAD-box RNA helicases facilitate mRNA unwinding for 40S subunit inspection.
Conclusions:
- Ribosomal scanning is a complex, multi-step process involving precise coordination of initiation factors and RNA helicases.
- The established model provides a framework for understanding how the ribosome selects the correct AUG start codon.
Related Concept Videos
02:28Leaky Scanning
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 stands for...
02:33Initiation of Translation
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...
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...
02:33Initiation of Translation
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...
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...
03:06From DNA to Protein
The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
02:07Improving Translational Accuracy
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...
01:25The Central Dogma
Overview