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- Architecture of the ribosome RNA-protein machine assembly
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2. Assembly of the 30S ribosomal subunit in vitro and in cells
- Prof. James Williamson
- Decoding and peptide bond formation
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3. How aminoacyl-tRNA synthetases translate the genetic code
- Dr. Stephen Cusack
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5. Elongation of protein synthesis: structural basis of the process of decoding
- Prof. Marina Rodnina
- Initiation of protein synthesis
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7. Factor independent initiation of protein synthesis by IRES RNAs
- Prof. Jeffrey Kieft
- Elongation and termination of protein synthesis
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8. Translocation: movement of tRNA and mRNA through the ribosome
- Prof. Harry Noller
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9. Recoding: getting more out of the message by shifting reading frame and redefining codon meaning
- Prof. John Atkins
- Prof. Raymond Gesteland
- Co-translational protein secretion
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10. Mechanism of translocon function: current insights and models
- Prof. Arnold Driessen
- How antibiotics target the ribosome
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12. Antibiotic inhibition of ribosome function
- Dr. Daniel Wilson
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13. Structure-based drug design targeting infectious disease
- Dr. Erin Duffy
- Archived Lectures *These may not cover the latest advances in the field
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15. Introduction to the ribosome
- Prof. Anders Liljas
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16. The structure of the intact ribosome and ribosomal subunit interactions
- Dr. Jamie H. Doudna Cate
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17. Structural insights into decoding of mRNA by the ribosome
- Prof. Venki Ramakrishnan
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18. Chemistry of peptide bond formation
- Prof. Rachel Green
Printable Handouts
Navigable Slide Index
- Introduction
- Why is initiation so important
- Two ways of translation initiation in eukaryotes
- Outline of the lecture
- Eukaryotic translation initiation
- Simple view of ribosome recruitment in eukaryotes
- Internal ribosome entry sites (IRESes)
- Some viral IRESes
- Single-stranded RNA virus replication cycle (HCV)
- Some cellular IRESes
- What specific RNA structures drive IRES function?
- Viral IRES mechanistic classes (1)
- Three IRES RNA secondary structures
- Cryo-EM reconstructions of IRES-40S complexes
- Ribosome manipulation by the HCV IRES
- Viral IRES mechanistic classes (2)
- Secondary structure of an IGR IRES
- IGR IRES - a manipulator of translation apparatus
- Hypothesis and questions
- Does IGR IRES have higher-order folded structure?
- Conservation among the IGR IRES folds
- The IGR IRES architecture
- Architecture of the IRES
- Solving the structure of two domains
- Crystal structure of the ribosome binding domain
- Crystal structure matches solution probing data
- Ribosome and IRES RNA specific contacts
- Mutant analysis confirms interaction with 60S
- Conserved bases in the IRES structure
- Differing mechanisms after 80S formation
- Structures of both domains were solved
- Structure of domain 3 / "P-site domain" of CrPV
- Pseudoknot mimics a codon-anticodon interaction
- Interactions that stabilize the structure
- Translation assays of IRES mutants
- The complete IRES on the 40S subunit
- Structure-based mechanism of IRES function
- Docking into ribosome+tRNA+mRNA structure
- Position of IRES domain and hybrid state tRNA
- The complete IRES on the ribosome
- Hypothesized tRNA hybrid state mimicry
- A complete and testable mechanistic model
- Conclusions
- Class I and class II IRESes are different
- Comparison with hepatitis C IRES
- Structures of HCV IRES domains
- Reviewing the lecture (1)
- Reviewing the lecture (2)
- Reviewing the lecture (3)
Topics Covered
- Translation initiation in eukaryotes: two pathways
- IRES-driven translation
- Types of IRESes
- IRES manipulation of ribosomes
- Folding and structure of the IGR IRESes
- IRES interactions with the ribosome and molecular mimicry
- New IRES mechanistic models
- Towards an understanding of more complex IRESes
- Update interview: Relationship of IRESs to other initiation mechanisms
- Update interview: Impact of diverse new techniques
- Update interview: Mechanistic insights from new structures
- Update interview: Future research directions and challenges
Talk Citation
Kieft, J. (2020, November 30). Factor independent initiation of protein synthesis by IRES RNAs [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved March 20, 2025, from https://doi.org/10.69645/UIEH5501.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Jeffrey Kieft has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Update Available
The speaker addresses developments since the publication of the original talk. We recommend listening to the associated update as well as the lecture.
- Full lecture Duration: 47:48 min
- Update Interview Duration: 8:23 min
Factor independent initiation of protein synthesis by IRES RNAs
A selection of talks on Cell Biology
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, my name is Dr. Jeffrey Kieft.
For the next portion of the series, understanding ribosomes,
I'm going to lecture on factor independent initiation of protein synthesis by IRES RNAs.
0:15
During the course of this lecture,
I'm going to talk about a mode of initiating
translation in eukaryotes with which you may not be familiar.
If you recall, the phase of translation in which the protein
making machinery is assembled is called the initiation step,
and this phase has special importance to the process of translation in general.
The reasons for this are many, but include fidelity.
That is, we want translation to begin at the right spot on the messenger RNA,
and not just at any AUG codon that the ribosome might find.
The speed at which translation occurs is also important,
because initiation is the rate-limiting step in translation.
The rate at which initiation occurs
determines how quickly a given amount of protein is made.
Finally, regulation.
Initiation is the primary phase for regulating translation.
Understanding how this important initiation process actually
happens is important if we're going to understand how ribosomes actually work.
1:14
Translation initiation in eukaryotes is
a stepwise ordered assembly process that is known to occur by one of two mechanisms.
The first mechanism is that which is used by the vast majority of messenger RNAs.
This is a cap-dependent, scanning-dependent mechanism,
which as its name implies,
depends on the presence of a 7-methylguanosine cap on the messenger RNA.
The second known mechanism for translation initiation is
a cap independent mechanism called internal initiation of translation.
We're going to talk about this more in detail, but for now,
what I want you to understand is that internal initiation is driven by
specific RNAs called internal ribosome entry sites or IRESes.
The lecture is going to be focused around three specific questions.