E. coli has the ability to regulate its enzymes to break down various sources of energy when available. It prevents waste by the use of the lac operon, which encodes a polycistronic transcript. At a low concentration of glucose and absence of lactose, which of the following occurs?
Q32
An investigator is following a 4-year-old boy with Duchenne muscular dystrophy. Western blot of skeletal muscle cells from this boy shows that the dystrophin protein is significantly smaller compared to the dystrophin protein of a healthy subject. Further evaluation shows that the boy's genetic mutation involves a sequence that normally encodes leucine. The corresponding mRNA codon has the sequence UUG. Which of the following codons is most likely present in this patient at the same position of the mRNA sequence?
Q33
A 62-year-old man with small cell lung cancer undergoes radiation therapy. His oncologist explains that radiation causes DNA damage and double strand breaks and this damage stops the cancer cells from growing because they can no longer replicate their DNA. One key mediator of this process is a cell cycle regulator called P53, which is upregulated after DNA damage and helps to trigger cell cycle arrest and apoptosis. One mechanism by which P53 activity is increased is a certain chromatin modification that loosens DNA coiling allowing for greater transcription of the proteins within that region of DNA. Which of the following enzymes most likely causes the chromatin modification described in this case?
Q34
A group of investigators is studying the effects of aberrant protein isoforms on the pathogenesis of lung cancer. They observe that three protein isoforms are transcribed from the same 30,160 base-pair-long DNA segment on chromosome 13q. The canonical protein has a primary peptide sequence of 1186 amino acids. The second isoform has 419 amino acids and 100% amino acid sequence homology with the canonical protein. The third isoform has 232 amino acids and 92% amino acid sequence homology with the canonical protein. Which of the following is most likely responsible for the observed phenomenon?
Q35
An 8-year-old boy is brought to the physician by his parents for blurry vision for the past 2 months. He is at the 97th percentile for height and 25th percentile for weight. Physical examination shows joint hypermobility, a high-arched palate, and abnormally long, slender fingers and toes. Slit lamp examination shows superotemporal lens subluxation bilaterally. This patient's findings are most likely caused by a defect in which of the following structural proteins?
Q36
An investigator is studying gene expression in a mouse model. She inactivates the assembly of small nuclear ribonucleoproteins (snRNPs) in motor nerve cells. Which of the following processes is most likely to be affected as a result?
Q37
A 24-year-old man is brought to the emergency department by his brother because of a 3-hour history of lethargy and confusion. The brother says that 2 days ago, the patient ate several large-capped mushrooms he had foraged in the woods. After eating the mushrooms, he developed severe, bloody diarrhea that has since resolved. His pulse is 140/min, respirations are 26/min, and blood pressure is 98/62 mm Hg. Examination shows dry mucous membranes and tenderness to deep palpation in the right upper quadrant. Serum studies show a serum AST concentration of 2335 U/L and ALT concentration of 2294 U/L. Inhibition of which of the following processes is the most likely cause of this patient's condition?
Q38
Given the mRNA sequence shown below, if translation were to start at the first base, what would the tRNA anticodon be for the last amino acid translated in the chain?
5'----GCACCGGCCUGACUAUAA---3'
Q39
An investigator is studying collagen synthesis in human fibroblast cells. Using a fluorescent tag, α-collagen chains are identified and then monitored as they travel through the rough endoplasmic reticulum, the Golgi apparatus, and eventually into the extracellular space. Which of the following steps in collagen synthesis occurs extracellularly?
Q40
A codon is an mRNA sequence consisting of 3 nucleotides that codes for an amino acid. Each position can be made up of any 4 nucleotides (A, U, G, C); therefore, there are a total of 64 (4 x 4 x 4) different codons that can be created but they only code for 20 amino acids. This is explained by the wobble phenomenon. One codon for leucine is CUU, which of the following can be another codon coding for leucine?
Transcription/translation US Medical PG Practice Questions and MCQs
Question 31: E. coli has the ability to regulate its enzymes to break down various sources of energy when available. It prevents waste by the use of the lac operon, which encodes a polycistronic transcript. At a low concentration of glucose and absence of lactose, which of the following occurs?
A. Decreased cAMP levels result in poor binding to the catabolite activator protein
B. Increased cAMP levels result in binding to the catabolite activator protein (Correct Answer)
C. Increased allolactose levels bind to the repressor
D. Repressor releases from lac operator
E. Transcription of the lac Z, Y, and A genes increase
Explanation: ***Increased cAMP levels result in binding to the catabolite activator protein***
- In the absence of glucose, **adenylate cyclase** activity increases, leading to higher levels of **cAMP**.
- **cAMP** then binds to the **catabolite activator protein (CAP)**, forming the **cAMP-CAP complex**, which is crucial for activating lac operon transcription in the absence of glucose.
*Decreased cAMP levels result in poor binding to the catabolite activator protein*
- **Decreased glucose levels** actually lead to **increased cAMP** synthesis, not decreased.
- High **cAMP** levels enhance, not hinder, its binding to **CAP**.
*Increased allolactose levels bind to the repressor*
- **Allolactose** is an inducer that forms in the presence of **lactose**, which is stated to be absent in this scenario.
- Therefore, **allolactose levels** would be low, and it would not bind to the **repressor**.
*Repressor releases from lac operator*
- The **repressor protein** is bound to the **lac operator** in the absence of lactose.
- For the **repressor to be released**, **allolactose** (formed from lactose) must be present to bind to it.
*Transcription of the lac Z, Y, and A genes increase*
- While **cAMP-CAP binding** would promote transcription, the **absence of lactose** means the **repressor remains bound** to the operator.
- This binding effectively blocks RNA polymerase, preventing significant transcription of the **lac Z, Y, and A genes**, regardless of high **cAMP** levels.
Question 32: An investigator is following a 4-year-old boy with Duchenne muscular dystrophy. Western blot of skeletal muscle cells from this boy shows that the dystrophin protein is significantly smaller compared to the dystrophin protein of a healthy subject. Further evaluation shows that the boy's genetic mutation involves a sequence that normally encodes leucine. The corresponding mRNA codon has the sequence UUG. Which of the following codons is most likely present in this patient at the same position of the mRNA sequence?
A. AUG
B. UCG
C. UAG (Correct Answer)
D. UUU
E. GUG
Explanation: ***UAG***
- A premature **stop codon** (UAG, UAA, UGA) leads to a truncated protein, which explains the significantly smaller dystrophin protein observed in the Western blot.
- The mutation converts a leucine codon (UUG) into a stop codon, resulting in a **nonsense mutation**.
*AUG*
- This codon codes for **methionine** and serves as the **start codon** for protein synthesis.
- A mutation from UUG to AUG would change one amino acid to another, but it would not result in a significantly smaller protein.
*UCG*
- This codon codes for **serine**.
- A mutation from UUG to UCG would result in a **missense mutation**, substituting leucine with serine, and would not lead to a significantly shorter protein.
*UUU*
- This codon codes for **phenylalanine**.
- A mutation from UUG to UUU would be a **missense mutation**, substituting leucine with phenylalanine, and would not cause protein truncation.
*GUG*
- This codon codes for **valine**.
- A mutation from UUG to GUG would result in a **missense mutation**, substituting leucine with valine, and would not lead to an abnormally short protein.
Question 33: A 62-year-old man with small cell lung cancer undergoes radiation therapy. His oncologist explains that radiation causes DNA damage and double strand breaks and this damage stops the cancer cells from growing because they can no longer replicate their DNA. One key mediator of this process is a cell cycle regulator called P53, which is upregulated after DNA damage and helps to trigger cell cycle arrest and apoptosis. One mechanism by which P53 activity is increased is a certain chromatin modification that loosens DNA coiling allowing for greater transcription of the proteins within that region of DNA. Which of the following enzymes most likely causes the chromatin modification described in this case?
A. Histone deacetylase
B. Histone acetyltransferase (Correct Answer)
C. Histone methyltransferase
D. DNA methyltransferase
E. Xist
Explanation: ***Histone acetyltransferase***
- This enzyme **acetylates histone proteins**, neutralizing their positive charge and thereby weakening their interaction with negatively charged DNA.
- This modification leads to a more **relaxed chromatin structure (euchromatin)**, making DNA more accessible for **transcription**, which is consistent with the upregulation of P53.
*Histone deacetylase*
- This enzyme **removes acetyl groups from histones**, making them more positively charged and increasing their affinity for DNA.
- This results in **condensed chromatin (heterochromatin)**, which generally **represses gene transcription**.
*Histone methyltransferase*
- This enzyme **adds methyl groups to histones**, which can either activate or repress gene transcription depending on the specific **lysine or arginine residue** methylated and the number of methyl groups added.
- While methylation is a chromatin modification, the question specifically describes a process of **loosening DNA coiling for greater transcription**, which is more characteristic of acetylation.
*DNA methyltransferase*
- This enzyme **adds methyl groups directly to DNA**, typically at **CpG sites**, leading to **gene silencing** by hindering transcription factor binding or recruiting repressor complexes.
- This modification primarily affects DNA directly, not histone proteins, and generally **inhibits gene expression**.
*Xist*
- **Xist (X-inactive specific transcript)** is a **long non-coding RNA** that plays a crucial role in **X-chromosome inactivation** in females.
- It functions by coating one of the X chromosomes, leading to its transcriptional silencing, rather than directly modifying chromatin for general gene upregulation.
Question 34: A group of investigators is studying the effects of aberrant protein isoforms on the pathogenesis of lung cancer. They observe that three protein isoforms are transcribed from the same 30,160 base-pair-long DNA segment on chromosome 13q. The canonical protein has a primary peptide sequence of 1186 amino acids. The second isoform has 419 amino acids and 100% amino acid sequence homology with the canonical protein. The third isoform has 232 amino acids and 92% amino acid sequence homology with the canonical protein. Which of the following is most likely responsible for the observed phenomenon?
A. Alternative pre-mRNA splicing (Correct Answer)
B. RNA interference
C. Post-translational protein trimming
D. Site-specific recombination
E. Cytosine hypermethylation
Explanation: ***Alternative pre-mRNA splicing***
- This process allows different combinations of **exons** from a single pre-mRNA to be included or excluded in the mature mRNA, leading to the production of multiple protein isoforms from one gene.
- The observation of three distinct protein isoforms with varying lengths (1186, 419, and 232 amino acids) that are **transcribed from the same DNA segment** strongly suggests that different parts of the original genetic information are being selectively utilized or excluded during mRNA processing.
- The **100% sequence homology** of the second isoform indicates it represents a subset of exons from the canonical protein, while the 92% homology of the third isoform suggests some alternative exon usage—both hallmarks of alternative splicing.
*RNA interference*
- **RNA interference** is primarily involved in **gene silencing** by inhibiting gene expression at the stage of translation or by preventing transcription.
- This mechanism would lead to a reduction or absence of protein production, not the creation of multiple distinct protein isoforms from the same gene.
*Post-translational protein trimming*
- **Post-translational modification**, such as protein trimming, involves enzymatic cleavage of a protein after it has been synthesized from a single mRNA transcript.
- While proteolytic cleavage can produce shorter protein fragments, it would not explain how these isoforms are **transcribed** as distinct entities from the same DNA segment. The description indicates these are separate mRNA products, not cleavage products of a single translated protein.
- Additionally, post-translational trimming alone cannot account for the **92% homology** observed in the third isoform, which suggests alternative sequence composition at the mRNA level.
*Site-specific recombination*
- **Site-specific recombination** involves precise DNA rearrangements to alter gene expression or generate diversity, as seen in **immunoglobulin gene recombination**.
- This process changes the DNA sequence itself and is not responsible for generating multiple protein isoforms from an intact, predefined DNA segment at the mRNA level.
*Cytosine hypermethylation*
- **Cytosine hypermethylation** is an epigenetic modification that typically leads to **gene silencing** by inhibiting transcription.
- This mechanism would reduce or prevent the expression of a gene, not produce multiple distinct protein isoforms with different lengths and sequences from a single gene.
Question 35: An 8-year-old boy is brought to the physician by his parents for blurry vision for the past 2 months. He is at the 97th percentile for height and 25th percentile for weight. Physical examination shows joint hypermobility, a high-arched palate, and abnormally long, slender fingers and toes. Slit lamp examination shows superotemporal lens subluxation bilaterally. This patient's findings are most likely caused by a defect in which of the following structural proteins?
A. Keratin
B. Fibrillin (Correct Answer)
C. Laminin
D. Type I collagen
E. Type III collagen
Explanation: ***Fibrillin***
- The patient's features—tall stature, **joint hypermobility**, high-arched palate, **arachnodactyly** (long, slender fingers and toes), and **superotemporal lens subluxation**—are classic signs of **Marfan syndrome**.
- Marfan syndrome is caused by a defect in the *FBN1* gene, which codes for **fibrillin-1**, a glycoprotein essential for the formation of elastic fibers in connective tissue.
*Keratin*
- **Keratins** are intermediate filament proteins primarily found in epithelial cells, providing structural integrity to skin, hair, and nails.
- Defects in keratin are associated with conditions like **epidermolysis bullosa simplex** and various **ichthyoses**, which manifest as skin fragility and blistering, not the systemic connective tissue issues seen here.
*Laminin*
- **Laminins** are major components of the **basement membrane**, providing structural support and mediating cell adhesion, differentiation, and migration.
- Disorders involving laminin typically affect organs with prominent basement membranes, such as certain muscular dystrophies or nephropathies, which do not align with the patient's symptoms.
*Type I collagen*
- **Type I collagen** is the most abundant collagen in the body, found in bone, skin, tendons, and ligaments, providing tensile strength.
- Defects in type I collagen are characteristic of **osteogenesis imperfecta**, leading to fragile bones, blue sclerae, and hearing loss, which are not described in this patient.
*Type III collagen*
- **Type III collagen** is found in distensible tissues like blood vessels, skin, and intestines, contributing to their elasticity and strength.
- Defects in type III collagen are associated with **Ehlers-Danlos syndrome, vascular type**, which typically presents with arterial rupture, thin skin, and easy bruising, distinct from the patient's presentation.
Question 36: An investigator is studying gene expression in a mouse model. She inactivates the assembly of small nuclear ribonucleoproteins (snRNPs) in motor nerve cells. Which of the following processes is most likely to be affected as a result?
A. Aminoacylation of tRNA
B. Removal of introns (Correct Answer)
C. Unwinding of DNA strands
D. Folding of proteins
E. Activity of 3′ to 5′ proofreading
Explanation: ***Removal of introns***
- **Small nuclear ribonucleoproteins (snRNPs)** are crucial components of the **spliceosome**, the molecular machinery responsible for **splicing**.
- **Splicing** is the process by which **introns** (non-coding regions) are removed from **pre-mRNA**, and exons (coding regions) are joined together to form mature mRNA.
*Aminoacylation of tRNA*
- **Aminoacylation of tRNA** involves attaching a specific transfer RNA molecule to its cognate amino acid, a process catalyzed by **aminoacyl-tRNA synthetases**.
- This process is essential for **protein synthesis** during translation but is independent of snRNPs.
*Unwinding of DNA strands*
- **Unwinding of DNA strands** occurs during DNA replication (by **helicase**) and transcription (by **RNA polymerase**) to allow access to the genetic information.
- These processes are distinct from splicing and do not directly involve snRNPs.
*Folding of proteins*
- **Protein folding** is a post-translational event, often facilitated by **chaperone proteins**, where a polypeptide chain acquires its specific three-dimensional structure.
- This process occurs after mRNA has been translated into a polypeptide and is not directly affected by snRNP function.
*Activity of 3′ to 5′ proofreading*
- **3′ to 5′ proofreading** is a function of **DNA polymerase** that ensures accuracy during DNA replication by excising incorrectly paired nucleotides.
- This mechanism is part of DNA synthesis and repair, completely separate from the role of snRNPs in RNA processing.
Question 37: A 24-year-old man is brought to the emergency department by his brother because of a 3-hour history of lethargy and confusion. The brother says that 2 days ago, the patient ate several large-capped mushrooms he had foraged in the woods. After eating the mushrooms, he developed severe, bloody diarrhea that has since resolved. His pulse is 140/min, respirations are 26/min, and blood pressure is 98/62 mm Hg. Examination shows dry mucous membranes and tenderness to deep palpation in the right upper quadrant. Serum studies show a serum AST concentration of 2335 U/L and ALT concentration of 2294 U/L. Inhibition of which of the following processes is the most likely cause of this patient's condition?
A. Parasympathetic activation
B. Messenger RNA synthesis (Correct Answer)
C. Microtubule polymerization
D. Cell depolarization
E. ATP production
Explanation: ***Messenger RNA synthesis***
- This patient's symptoms, including **severe gastrointestinal upset** followed by apparent recovery and then **hepatic encephalopathy** (lethargy, confusion, elevated AST/ALT), are classic for **Amanita phalloides (death cap mushroom) poisoning**.
- The primary toxin, **α-amanitin**, specifically inhibits **RNA polymerase II**, thereby blocking **mRNA synthesis** and leading to hepatocyte death and liver failure.
*Parasympathetic activation*
- This is characteristic of poisoning by muscarinic agonists (e.g., *Inocybe* or *Clitocybe* mushrooms), causing symptoms like **salivation, lacrimation, urination, defecation, gastrointestinal cramping, and emesis (SLUDGE)**.
- While initial GI symptoms might overlap, the severe liver damage and delayed presentation of encephalopathy are inconsistent with sole parasympathetic overactivation.
*Microtubule polymerization*
- Inhibition of microtubule polymerization is associated with toxins like **colchicine** or **vincristine**, which can cause gastrointestinal toxicity and myelosuppression.
- It does not directly explain the severe hepatotoxicity and delayed onset of liver failure seen in this patient.
*Cell depolarization*
- This mechanism is associated with neurotoxins that affect ion channels, such as those found in some species of *Gyromitra* mushrooms (producing **monomethylhydrazine**) or *Psilocybe* (containing **psilocybin**).
- While neurotoxicity can occur, the prominent and severe liver failure points away from cell depolarization as the primary mechanism in this case.
*ATP production*
- Toxins that inhibit ATP production (e.g., cyanide, carbon monoxide, some mitochondrial poisons) cause widespread cellular dysfunction and can lead to multi-organ failure.
- While severe liver failure will eventually impair ATP production, α-amanitin's direct mechanism is earlier in the protein synthesis pathway (mRNA synthesis), leading to a delayed, but profound, impact on cellular function and viability.
Question 38: Given the mRNA sequence shown below, if translation were to start at the first base, what would the tRNA anticodon be for the last amino acid translated in the chain?
5'----GCACCGGCCUGACUAUAA---3'
A. 3' GCG 5'
B. 3' CGC 5'
C. 5' CGG 3'
D. 3' CGG 5' (Correct Answer)
E. 3' GAU 5'
Explanation: ***3' CGG 5'***
- The mRNA sequence is 5'-GCACCGGCCUGACUAUAA-3'. We need to identify the **open reading frame** starting from the first base and translate codons until a stop codon is reached.
- The codons are **GCA** (Ala), **CCG** (Pro), **GCC** (Ala), **UGA** (Stop). The **last amino acid** translated is Alanine, corresponding to the mRNA codon **GCC**. The tRNA anticodon for GCC is **3'-CGG-5'** because base pairing rules dictate C pairs with G, and G pairs with C, in an antiparallel orientation.
*3' GCG 5'*
- This anticodon would pair with an mRNA codon of 5'-CGC-3', which codes for Arginine, not the alanine derived from the last amino acid in the given sequence.
- It does not correctly reflect the antiparallel binding and base pairing required for the mRNA codon GCC.
*5' CGG 3'*
- While it contains the correct bases for pairing with GCC, the **orientation is incorrect**. tRNA anticodons are written 3' to 5'.
- A 5'-CGG-3' anticodon would pair with an mRNA codon of 3'-GCC-5', which is not consistent with the standard 5' to 3' mRNA codon reading.
*3' GAU 5'*
- This anticodon would pair with an mRNA codon of 5'-CUA-3', which codes for Leucine.
- Leucine is not the last amino acid translated from the given mRNA sequence before a stop codon.
*3' CGC 5'*
- This anticodon would pair with an mRNA codon of 5'-GCG-3', which codes for Alanine.
- However, the last amino acid translated is encoded by 5'-GCC-3', not 5'-GCG-3'.
Question 39: An investigator is studying collagen synthesis in human fibroblast cells. Using a fluorescent tag, α-collagen chains are identified and then monitored as they travel through the rough endoplasmic reticulum, the Golgi apparatus, and eventually into the extracellular space. Which of the following steps in collagen synthesis occurs extracellularly?
A. Triple-helix formation
B. Translation of pro-α chains
C. Cleavage of procollagen C- and N-terminals (Correct Answer)
D. Glycosylation of pro-α chains
E. Hydroxylation of proline and lysine
Explanation: ***Cleavage of procollagen C- and N-terminals***
- After procollagen is secreted into the extracellular space, specific **proteolytic enzymes** (procollagen peptidases) cleave the bulky N- and C-terminal propeptides.
- This cleavage transforms procollagen into insoluble **tropocollagen** molecules, which then spontaneously self-assemble into collagen fibrils.
*Triple-helix formation*
- This crucial step occurs within the **rough endoplasmic reticulum (RER)**, after hydroxylation and glycosylation of pro-α chains.
- The three pro-α chains intertwine to form a stable, rod-like **procollagen molecule**.
*Translation of pro-α chains*
- The synthesis of pro-α chains (polypeptide chains) takes place on **ribosomes** attached to the **rough endoplasmic reticulum (RER)**.
- This process is initiated in the cytosol and completed *into* the lumen of the RER.
*Glycosylation of pro-α chains*
- The addition of specific **oligosaccharide units** to hydroxylysine residues occurs in the **rough endoplasmic reticulum (RER)** and **Golgi apparatus**.
- This modification is important for the stability of the collagen triple helix and for interactions with other extracellular matrix components.
*Hydroxylation of proline and lysine*
- This post-translational modification, essential for the stability of the collagen triple helix, occurs in the **rough endoplasmic reticulum (RER)**.
- Enzymes like **prolyl hydroxylase** and **lysyl hydroxylase** require **vitamin C** as a cofactor for this reaction.
Question 40: A codon is an mRNA sequence consisting of 3 nucleotides that codes for an amino acid. Each position can be made up of any 4 nucleotides (A, U, G, C); therefore, there are a total of 64 (4 x 4 x 4) different codons that can be created but they only code for 20 amino acids. This is explained by the wobble phenomenon. One codon for leucine is CUU, which of the following can be another codon coding for leucine?
A. CUA (Correct Answer)
B. CCC
C. UAA
D. CCA
E. AUG
Explanation: ***CUA***
- The **wobble hypothesis** allows for non-standard base pairing at the **third position** of the codon.
- Since CUU codes for leucine, a change in the third base to **A (CUA)** can often still code for the same amino acid due to degeneracy of the genetic code.
*CCC*
- This codon codes for **proline**, not leucine.
- A change in the **second letter** of the codon almost always results in a different amino acid.
*UAA*
- This is one of the **stop codons** (UAA, UAG, UGA), which signals the termination of translation.
- It does not code for any amino acid.
*CCA*
- This codon codes for **proline**, not leucine.
- Changing the first or second nucleotide typically results in a different amino acid.
*AUG*
- This codon codes for **methionine** and also serves as the **start codon** for protein synthesis.
- It does not code for leucine.
