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Questions and Answers
What role does phosphatidylinositol 3 kinase (PI3K) play in the signaling process?
What role does phosphatidylinositol 3 kinase (PI3K) play in the signaling process?
How does AKT contribute to protein synthesis in cells?
How does AKT contribute to protein synthesis in cells?
Which process occurs when the AKT-mTOR pathway is mutated?
Which process occurs when the AKT-mTOR pathway is mutated?
What is a consequence of normal mRNA decay?
What is a consequence of normal mRNA decay?
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What is the role of exoribonucleases in mRNA decay?
What is the role of exoribonucleases in mRNA decay?
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What mechanism allows specific control over mRNA translation and stability?
What mechanism allows specific control over mRNA translation and stability?
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What happens to the 40S ribosomal subunit during protein synthesis in the presence of starvation?
What happens to the 40S ribosomal subunit during protein synthesis in the presence of starvation?
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What effect does hyperactivity of the AKT-mTOR pathway have on cellular behavior?
What effect does hyperactivity of the AKT-mTOR pathway have on cellular behavior?
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What is the primary function of the peptidyl transferase reaction?
What is the primary function of the peptidyl transferase reaction?
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Which step in translation is most frequently targeted for regulation?
Which step in translation is most frequently targeted for regulation?
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How does the 40S ribosomal subunit first interact with mRNA during initiation?
How does the 40S ribosomal subunit first interact with mRNA during initiation?
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What is the role of the 60S subunit in translation initiation?
What is the role of the 60S subunit in translation initiation?
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What is the significance of the 'modified scanning hypothesis'?
What is the significance of the 'modified scanning hypothesis'?
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What crucial role does iron play in the body?
What crucial role does iron play in the body?
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What does the control of ferritin synthesis illustrate about translation regulation?
What does the control of ferritin synthesis illustrate about translation regulation?
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What characterizes the translation initiation process in viral RNAs?
What characterizes the translation initiation process in viral RNAs?
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What is formed after the larger pri-miRNA folds back on itself?
What is formed after the larger pri-miRNA folds back on itself?
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What role does the protein argonaute (Ago) play in the miRNA process?
What role does the protein argonaute (Ago) play in the miRNA process?
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How do microRNAs (miRNAs) contribute to gene expression regulation?
How do microRNAs (miRNAs) contribute to gene expression regulation?
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What happens to the passenger strand after miRNA processing by dicer?
What happens to the passenger strand after miRNA processing by dicer?
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What type of cell processes the entry of the COVID-19 virus?
What type of cell processes the entry of the COVID-19 virus?
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Which of the following diseases have been linked to genes encoding microRNAs?
Which of the following diseases have been linked to genes encoding microRNAs?
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What is the initial action of the COVID-19 virus once it enters a host cell?
What is the initial action of the COVID-19 virus once it enters a host cell?
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What is the role of the viral encoded replicase in the COVID-19 infection process?
What is the role of the viral encoded replicase in the COVID-19 infection process?
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What primarily causes the progressive loss of muscle function in DMD?
What primarily causes the progressive loss of muscle function in DMD?
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Why are females usually less severely affected by DMD?
Why are females usually less severely affected by DMD?
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What is the size of the dystrophin mRNA encoded by the DMD gene?
What is the size of the dystrophin mRNA encoded by the DMD gene?
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Where are many DMD-causing mutations located?
Where are many DMD-causing mutations located?
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What is a likely outcome of encountering a premature termination codon?
What is a likely outcome of encountering a premature termination codon?
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What is the probability of encountering a stop codon due to a translational reading frame-shift mutation?
What is the probability of encountering a stop codon due to a translational reading frame-shift mutation?
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What happens to truncated proteins in a cell?
What happens to truncated proteins in a cell?
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What syndrome is an exception that allows females carrying a DMD mutation to be severely affected?
What syndrome is an exception that allows females carrying a DMD mutation to be severely affected?
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What is the primary function of microRNAs in relation to mRNA?
What is the primary function of microRNAs in relation to mRNA?
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In which part of the mRNA are miRNA recognition sequences typically located?
In which part of the mRNA are miRNA recognition sequences typically located?
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What initiates the process of microRNA synthesis?
What initiates the process of microRNA synthesis?
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What is the RNA silencing complex more commonly known as?
What is the RNA silencing complex more commonly known as?
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How many microRNAs have been identified in humans since the initial discovery?
How many microRNAs have been identified in humans since the initial discovery?
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What common source led to the discovery of human microRNAs?
What common source led to the discovery of human microRNAs?
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What is the role of the seed sequence in a microRNA?
What is the role of the seed sequence in a microRNA?
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What can happen once the RISC complex binds to its target mRNA?
What can happen once the RISC complex binds to its target mRNA?
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Study Notes
Peptidyl Transferase Reaction
- Essential biochemical reaction for protein synthesis where protein-encoding sequences in the genome guide the production of proteins.
Translation Initiation
- Most regulated step in translation.
- 40S ribosomal subunit accesses mRNA via the 7-MeG cap or through internal entry to find the start codon (AUG).
- Internal entry often occurs with viral RNAs lacking a cap but can also happen with some cellular mRNAs.
- The 40S subunit scans mRNA in the 5’ to 3’ direction to locate the AUG start codon.
- Joins with 60S subunit to form an 80S ribosome, allowing for protein synthesis.
Scanning Hypothesis
- Originally proposed that the 40S subunit selects the first encountered AUG for translation initiation.
- Modified scanning hypothesis emphasizes the importance of surrounding bases for proper context of the start codon.
Regulation of Translation: Ferritin Synthesis
- Ferritin regulates iron storage to prevent toxicity from free iron.
- Growth factor binds a receptor activating phosphatidylinositol 3 kinase (PI3K), triggering downstream signaling pathways.
- Activated AKT and mTOR enhance ribosomal protein synthesis and ribosome biogenesis.
- AKT-mTOR signaling facilitates 40S ribosomal subunit access at the 7-MeG cap, promoting cap-dependent translation.
mRNA Stability Regulation
- mRNA decay occurs when transcripts are no longer needed, varying from hours to longer translations.
- Regulatory sites in the 3’ UTR promote instability for mRNAs needing low protein levels.
- Exoribonucleases degrade mRNA, either from the 5’ end (decapping) or 3’ end (poly(A) tail removal).
Role of MicroRNAs (miRNAs)
- Small noncoding RNAs that regulate gene expression post-transcriptionally.
- First discovered in C.elegans; humans have over 2,000 identified miRNAs.
- Each miRNA contains a "seed sequence" that binds complementary mRNA sequences, often in the 3’ UTR.
- miRNAs inhibit translation or degrade mRNAs through the RNA-induced silencing complex (RISC).
MicroRNA Synthesis Pathways
- miRNAs derive from larger precursor transcripts (pri-miRNAs) or from splicing of introns.
- Processed in the nucleus and cytoplasm into active miRNA, which binds Argonaute (Ago) proteins to target mRNAs.
Importance of miRNAs
- Critical for regulation of cell differentiation, growth, and development; especially relevant in stem cell regulation.
- Involved in various diseases, including cancer, with distinct expression profiles for different tumors.
COVID-19 Virus Propagation
- The virus targets ACE2 receptors in the respiratory tract via its spike protein, followed by endocytosis.
- Releases its single-stranded RNA genome that is translated by the host’s machinery to replicate and package viral genomes.
Dystrophin Gene and Dystrophic Muscle Disorders
- Dystrophin gene linked to DMD (Duchenne Muscular Dystrophy), primarily affecting boys due to X-linked inheritance.
- Encodes the largest mRNA (over 2.5 million bases) with critical mutations affecting splice sites.
- Premature termination codons caused by intron retention or improperly spliced exons lead to truncated, non-functional proteins, disrupting cellular metabolism.
Premature Termination Codons
- Only three termination codons: UAA, UGA, UAG, among 64 total codons.
- Insertion/deletion mutations yield a 1 in 20 chance of encountering a premature stop codon, leading to truncated proteins that can compete with full-length variants and impair cell function.
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Description
This quiz explores the peptidyl transferase reaction, a crucial biochemical process that facilitates protein synthesis from genomic sequences. It focuses on the initiation stage of translation and its regulatory aspects, particularly the role of the 40S ribosomal subunit. Test your understanding of these fundamental concepts in biochemistry.