Transcription/translation

Transcription/translation US Medical PG Question 1: 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

Transcription/translation 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.

Transcription/translation US Medical PG Question 2: An investigator is comparing DNA replication in prokaryotes and eukaryotes. He finds that the entire genome of E. coli (4 × 106 base pairs) is replicated in approximately 30 minutes. A mammalian genome (3 × 109 base pairs) is usually replicated within 3 hours. Which of the following characteristics of eukaryotic DNA replication is the most accurate explanation for this finding?

• A. Replication inhibition at checkpoint
• B. Absence of telomerase enzyme activity
• C. DNA compaction in chromatin
• D. Simultaneous replication at multiple origins (Correct Answer)
• E. More efficient DNA polymerase activity

Transcription/translation Explanation: ***Simultaneous replication at multiple origins*** - Eukaryotic DNA replication initializes at **multiple origins of replication** along each chromosome, allowing synthesis to occur concurrently in many places. - This strategy compensates for the much larger eukaryotic genome size, enabling its complete replication within a reasonable timeframe despite slower polymerase speed compared to prokaryotes. *Replication inhibition at checkpoint* - **Cell cycle checkpoints**, such as those in G1, S, and G2 phases, ensure the integrity of DNA replication and repair. - While these checkpoints can *pause* or *inhibit* replication if errors occur, they do not fundamentally explain the *speed* or **efficiency** of replication across the entire genome. *Absence of telomerase enzyme activity* - **Telomerase** is an enzyme that maintains the ends of eukaryotic chromosomes (telomeres) by adding repetitive DNA sequences. - Its presence or absence is related to telomere length regulation and cellular aging, not the overall speed of genome replication. *DNA compaction in chromatin* - Eukaryotic DNA is compact and organized into **chromatin** within the nucleus, which presents a challenge to replication by limiting access to the DNA. - While enzymes must overcome this compaction, it is a *hindrance* rather than an enabler of replication speed. If anything, it would slow down replication. *More efficient DNA polymerase activity* - In actuality, **prokaryotic DNA polymerases** (e.g., DNA Pol III in *E. coli*) are generally more processive and faster than eukaryotic DNA polymerases. - Therefore, more efficient polymerase activity is not a characteristic that would explain the relatively fast replication of a larger eukaryotic genome.

Transcription/translation US Medical PG Question 3: An investigator studying protein synthesis in human stem cells isolates tRNA molecules bound to mRNA molecules. The isolated tRNA molecules have inosine in the 5' position of the anticodon; of these, some are bound to adenine, some to cytosine, and some to uracil at the 3' position of the mRNA codon. Which of the following properties of the genetic code is best illustrated by this finding?

• A. Unambiguity
• B. Non-overlapping
• C. Degeneracy (Correct Answer)
• D. Specificity of the start codon
• E. Specificity of stop codons

Transcription/translation Explanation: ***Degeneracy*** - The finding that a single tRNA anticodon (with **inosine** at the 5' position) can bind to multiple different mRNA codons (ending in **adenine, cytosine, or uracil**) illustrates the concept of **degeneracy** in the genetic code. - This **wobble hypothesis** allows fewer tRNAs to recognize more than one codon for a given amino acid, meaning multiple codons can code for the same amino acid. *Unambiguity* - The genetic code is unambiguous, meaning that each codon specifies **only one specific amino acid** (or a stop signal) and never two different amino acids. - This finding, however, shows one tRNA recognizing multiple codons, not one codon coding for multiple amino acids. *Non-overlapping* - The **non-overlapping** nature of the genetic code means that each nucleotide in an mRNA sequence is read only once as part of a single codon, without sharing nucleotides between adjacent codons. - This concept describes how codons are read sequentially, not the flexibility of codon-anticodon pairing. *Specificity of the start codon* - The **start codon (AUG)** specifically initiates translation, coding for methionine, and signals the beginning of a polypeptide chain. - This finding relates to the wobble pairing at the 3' end of the codon, not the initiation of translation. *Specificity of stop codons* - **Stop codons (UAA, UAG, UGA)** specifically signal the termination of translation without coding for any amino acid. - This finding describes the flexibility of codon-anticodon pairing, not the distinct function of termination codons.

Transcription/translation US Medical PG Question 4: An 18-year-old African-American woman comes to the physician for the evaluation of worsening fatigue that started 1 year ago. Physical examination shows mild jaundice and splenomegaly. Laboratory studies show: Hemoglobin 10.4 g/dL Mean corpuscular hemoglobin concentration 43% Hb/cell Platelet count 220,000/mm3 Reticulocyte count 7% A peripheral blood smear shows target cells and erythrocytes with hemoglobin crystals. Which of the following is the most likely underlying cause of this patient's findings?

• A. Acquired mutation of membrane-bound glycosylphosphatidylinositol anchor
• B. Decreased conversion of oxidized glutathione into its reduced form
• C. Replacement of glutamate by valine in beta-globin chain
• D. Replacement of glutamate by lysine in beta-globin chain (Correct Answer)
• E. Reduced production of beta-globin due to a mutation in the HbB gene

Transcription/translation Explanation: ***Replacement of glutamate by lysine in beta-globin chain*** - The combination of **mild jaundice**, **splenomegaly**, **anemia**, **elevated reticulocyte count**, and the presence of **target cells** and **hemoglobin C crystals** on peripheral smear is characteristic of **Hemoglobin C disease**. - **Hemoglobin C** results from the **replacement of glutamate by lysine at position 6 of the beta-globin chain**, leading to abnormal hemoglobin and erythrocyte morphology. *Acquired mutation of membrane-bound glycosylphosphatidylinositol anchor* - This describes **Paroxysmal Nocturnal Hemoglobinuria (PNH)**, which is characterized by **hemolytic anemia**, **thrombosis**, and **bone marrow failure**. - While it causes hemolytic anemia, the peripheral smear findings of **target cells** and **hemoglobin crystals** are not typical for PNH as seen in this patient. *Decreased conversion of oxidized glutathione into its reduced form* - This mechanism is characteristic of **Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency**, a cause of **hemolytic anemia**. - G6PD deficiency typically presents with episodic hemolysis triggered by **oxidative stress**, and the characteristic peripheral smear findings are **Heinz bodies** and **bite cells**, not hemoglobin crystals. *Replacement of glutamate by valine in beta-globin chain* - This mutation describes **Sickle Cell Anemia**, which also causes hemolytic anemia and splenomegaly. - While it leads to **sickle cells** on peripheral smear, **hemoglobin C crystals** and **target cells** are not the primary features; sickle cells and Howell-Jolly bodies would be expected. *Reduced production of beta-globin due to a mutation in the HbB gene* - This describes **Beta-thalassemia**, a group of disorders characterized by **reduced or absent beta-globin chain synthesis**. - Beta-thalassemia typically presents with **microcytic hypochromic anemia** and **target cells**, but the presence of **hemoglobin C crystals** is not a feature.

Transcription/translation US Medical PG Question 5: In translation, the wobble phenomenon is best illustrated by the fact that:

• A. Charged tRNA contains energy needed for peptide bonds to form
• B. The last nucleotide provides specificity for the given amino acid
• C. A tRNA with the UUU anticodon can bind to either AAA or AAG codons (Correct Answer)
• D. There are more amino acids than possible codons
• E. The genetic code is preserved without mutations

Transcription/translation Explanation: ***A tRNA with the UUU anticodon can bind to either AAA or AAG codons*** - The **wobble phenomenon** allows for non-standard base pairing between the **first nucleotide (5' position) of the tRNA anticodon** and the **third nucleotide (3' position) of the mRNA codon**. - In this example, a tRNA with anticodon **3'-UUU-5'** can bind to either **5'-AAA-3'** or **5'-AAG-3'** codons (both encoding lysine) due to the relaxed base-pairing rules at the wobble position. - This flexibility means fewer tRNAs are needed to recognize all 61 sense codons, illustrating the **degeneracy of the genetic code**. - According to Crick's wobble hypothesis, **U at the 5' position of the anticodon** can pair with either **A or G at the 3' position of the codon**. *Charged tRNA contains energy needed for peptide bonds to form* - While **charged tRNA** (aminoacyl-tRNA) does carry an amino acid activated for peptide bond formation, this statement describes the energy source for translation, not the wobble phenomenon. - The energy for peptide bond formation comes from the **high-energy ester bond** linking the amino acid to the tRNA, not from the base pairing itself. *The last nucleotide provides specificity for the given amino acid* - The **last nucleotide** (3' position) of the mRNA codon is where **wobble pairing** occurs, meaning it does *not* always provide strict specificity for the amino acid due to the relaxed base-pairing rules. - It is often the *first two nucleotides* of the codon that are most critical in determining the specific amino acid incorporated. *There are more amino acids than possible codons* - This statement is incorrect; there are **20 standard amino acids** and **61 sense codons** (three are stop codons), meaning there are more codons than amino acids, leading to **code degeneracy**. - The concept of wobble base pairing helps explain how this degeneracy is managed efficiently, but the premise of this option is false. *The genetic code is preserved without mutations* - This statement refers to the **fidelity of DNA replication and repair** or the evolutionary conservation of the genetic code, not the mechanism of translation or wobble base pairing. - The genetic code being largely universal and degenerate does not mean that mutations never occur, but rather that it is robust.

Transcription/translation US Medical PG Question 6: An investigator is studying the genetic profile of an isolated pathogen that proliferates within macrophages. The pathogen contains sulfatide on the surface of its cell wall to prevent fusion of the phagosome and lysosome. She finds that some of the organisms under investigation have mutations in a gene that encodes the enzyme required for synthesis of RNA from a DNA template. The mutations are most likely to reduce the therapeutic effect of which of the following drugs?

• A. Pyrazinamide
• B. Ethambutol
• C. Rifampin (Correct Answer)
• D. Streptomycin
• E. Levofloxacin

Transcription/translation Explanation: ***Rifampin*** - **Rifampin** specifically targets bacterial **DNA-dependent RNA polymerase**, inhibiting **RNA synthesis**. Mutations in the gene encoding this enzyme would directly reduce rifampin's binding and effectiveness. - The description of the pathogen thriving within macrophages and using **sulfatide to evade lysosomal fusion** strongly suggests **Mycobacterium tuberculosis**, a bacterium for which rifampin is a cornerstone treatment. *Pyrazinamide* - **Pyrazinamide** is a prodrug that, once converted to **pyrazinoid acid**, disrupts **mycobacterial membrane potential** and metabolism. Its primary target is not RNA synthesis. - Its efficacy is pH-dependent and it acts optimally in acidic environments, such as within macrophages, but mutations affecting RNA synthesis would not directly compromise its action. *Ethambutol* - **Ethambutol** inhibits **arabinosyl transferase**, an enzyme essential for the synthesis of the **mycobacterial cell wall component arabinogalactan**. - Its mechanism of action is distinct from RNA synthesis, thus mutations affecting RNA polymerase would not impact its efficacy. *Streptomycin* - **Streptomycin** is an **aminoglycoside antibiotic** that binds to the **30S ribosomal subunit**, inhibiting bacterial **protein synthesis**. - This mechanism is unrelated to DNA-dependent RNA polymerase, so mutations in RNA synthesis enzymes would not affect streptomycin's action. *Levofloxacin* - **Levofloxacin** is a **fluoroquinolone antibiotic** that inhibits **bacterial DNA gyrase (topoisomerase II)** and **topoisomerase IV**, thereby blocking DNA replication and transcription. - While it affects processes related to DNA, its direct target is not the DNA-dependent RNA polymerase enzyme itself, distinguishing it from rifampin's specific mechanism.

Transcription/translation US Medical PG Question 7: A clinical trial is being run with patients that have a genetic condition characterized by abnormal hemoglobin that can undergo polymerization when exposed to hypoxia, acidosis, or dehydration. This process of polymerization is responsible for the distortion of the red blood cell (RBC) that acquires a crescent shape and the hemolysis of RBCs. Researchers are studying the mechanisms of the complications commonly observed in these patients such as stroke, aplastic crisis, and auto-splenectomy. What kind of mutation leads to the development of the disease?

• A. Silent mutation
• B. Splice site
• C. Missense mutation (Correct Answer)
• D. Nonsense mutation
• E. Frameshift mutation

Transcription/translation Explanation: ***Missense mutation*** - A missense mutation results in a **single nucleotide substitution** that changes the codon to code for a different amino acid, altering the protein. - In **sickle cell disease**, a missense mutation in the beta-globin gene (GAG to GTG) leads to the substitution of **glutamic acid for valine**, causing abnormal hemoglobin (HbS) that polymerizes under deoxygenated conditions. *Silent mutation* - A silent mutation is a **point mutation** that results in a new codon that still codes for the **same amino acid**, meaning there is no change in the protein sequence. - Therefore, it would not lead to an **abnormal hemoglobin** protein or the described disease phenotype. *Splice site* - A splice site mutation occurs at the **splice junctions** of introns and exons, leading to errors in mRNA processing. - This can result in **incorrect protein synthesis** due to exon skipping or intron retention, but it typically does not cause the specific amino acid substitution seen in sickle cell disease. *Nonsense mutation* - A nonsense mutation is a point mutation that results in a **premature stop codon**, leading to a **truncated, non-functional protein**. - While this can cause severe disease, it would typically lead to a complete absence or severe deficiency of functional hemoglobin rather than a structurally altered hemoglobin like HbS. *Frameshift mutation* - A frameshift mutation involves the **insertion or deletion of nucleotides** (not in multiples of three), which shifts the reading frame of the mRNA. - This typically leads to a completely **altered amino acid sequence** downstream of the mutation and usually results in a premature stop codon, leading to a non-functional protein rather than a specific single amino acid substitution.

Transcription/translation US Medical PG Question 8: A mutant stem cell was created by using an inducible RNAi system, such that when doxycycline is added, the siRNA targeting DNA helicase is expressed, effectively knocking down the gene for DNA helicase. Which of the following will occur during DNA replication?

• A. The RNA primer is not created
• B. DNA is not unwound (Correct Answer)
• C. The two melted DNA strands reanneal
• D. DNA supercoiling is not relieved
• E. Newly synthesized DNA fragments are not ligated

Transcription/translation Explanation: ***DNA is not unwound*** - **DNA helicase** is essential for unwinding the **double-stranded DNA** helix, separating it into two single strands. This process creates the **replication fork**. - Without functional DNA helicase due to **gene knockdown**, the DNA helix cannot be unwound, thus halting DNA replication. *The RNA primer is not created* - **RNA primers** are synthesized by **primase**, an enzyme distinct from DNA helicase. - While unwinding is necessary for primer synthesis, the *creation* of the primer itself is a function of primase. *The two melted DNA strands reanneal* - **Reannealing** of DNA strands is prevented by **single-strand binding proteins (SSBs)**, which bind to the separated single strands. - While helicase unwinds, SSBs specifically keep the strands apart to allow DNA polymerase access. *DNA supercoiling is not relieved* - **DNA supercoiling** is relieved by **topoisomerases**, enzymes that cut, unwind, and religate DNA strands to reduce torsional stress. - This is a distinct function from DNA helicase, which focuses on breaking hydrogen bonds between strands. *Newly synthesized DNA fragments are not ligated* - **Ligation** of newly synthesized **Okazaki fragments** on the lagging strand is performed by **DNA ligase**. - This process occurs downstream from the unwinding step facilitated by DNA helicase.

Transcription/translation US Medical PG Question 9: An investigator is studying the incidence of sickle cell trait in African American infants. To identify the trait, polymerase chain reaction testing is performed on venous blood samples obtained from the infants. Which of the following is required for this laboratory technique?

• A. Single-stranded binding proteins
• B. Ligation of Okazaki fragments
• C. Primers complementary to target DNA sequences (Correct Answer)
• D. Complete genome DNA sequence
• E. RNA-dependent DNA polymerase

Transcription/translation Explanation: ***Primers complementary to target DNA sequences*** - **Primers** are short, synthetic single-stranded DNA sequences that **bind specifically** to the flanking regions of the target DNA sequence to be amplified. - In PCR, these primers define the **start and end points** of the DNA segment that will be copied, allowing for the exponential amplification of a specific region of interest. *Single-stranded binding proteins* - **Single-stranded binding proteins (SSBs)** are crucial in **DNA replication** to stabilize unwound single-stranded DNA and prevent re-annealing or degradation. - They are generally **not required** in standard PCR as the DNA strands are separated by heat denaturation, and the rapid cooling in primer annealing prevents re-annealing of the entire template. *Ligation of Okazaki fragments* - **Okazaki fragments** are short DNA segments synthesized on the **lagging strand** during **DNA replication**. - Their ligation by **DNA ligase** is a key step in DNA replication, but it is **not part of the PCR process**, which synthesizes DNA continuously from primers. *Complete genome DNA sequence* - While knowing the **complete genome sequence** of an organism would be helpful for understanding the entire genetic makeup, it is **not a prerequisite** for performing PCR. - PCR only requires knowledge of the **short flanking sequences** where the primers will bind to amplify a specific gene or region. *RNA-dependent DNA polymerase* - **RNA-dependent DNA polymerase**, also known as **reverse transcriptase**, is used to synthesize DNA from an RNA template in **reverse transcription PCR (RT-PCR)**. - While RT-PCR is a variant of PCR, standard PCR, as described for identifying a genetic trait in DNA, **does not require this enzyme**; instead, it uses a **DNA-dependent DNA polymerase** (e.g., Taq polymerase).

Transcription/translation US Medical PG Question 10: A 12-year-old male presents to the emergency department following several days of facial edema. A urinalysis confirms proteinuria and hematuria. Once admitted, a kidney biopsy is viewed under an electron microscope to confirm the diagnosis of minimal change disease. In the following electron micrograph, what process occurs in the structure marked with an arrow?

• A. Podocyte foot process effacement (Correct Answer)
• B. Normal podocyte foot process interdigitation
• C. Mesangial cell proliferation
• D. Endothelial cell fenestration
• E. Glomerular basement membrane thickening

Transcription/translation Explanation: **Podocyte foot process effacement** - Minimal change disease is characterized by the **effacement (flattening and fusion)** of podocyte foot processes, which are the structures indicated by the arrow in the image. - This effacement leads to the loss of the **slit diaphragm barrier**, causing massive proteinuria. *Normal podocyte foot process interdigitation* - Normal podocyte foot processes exhibit a distinct, highly organized **interdigitating pattern**, which is clearly not observed in the image due to the flattening. - This normal interdigitation is crucial for maintaining the **glomerular filtration barrier** and preventing protein leakage. *Mesangial cell proliferation* - **Mesangial cell proliferation** is characteristic of conditions like IgA nephropathy or mesangioproliferative glomerulonephritis, and is not the primary feature of minimal change disease. - The image illustrates changes in the podocytes, not the mesangial cells (labeled 'M'). *Endothelial cell fenestration* - **Endothelial cell fenestrations** are normal pores in the glomerular endothelial cells that allow for filtration, and are not directly affected or effaced in minimal change disease. - The arrow in the image points to the podocyte layer, not the endothelial cells. *Glomerular basement membrane thickening* - **Glomerular basement membrane (GBM) thickening** is seen in conditions like diabetic nephropathy or membranous nephropathy, but not typically in minimal change disease. - In minimal change disease, the GBM typically appears normal under electron microscopy.

Transcription/translation Flashcard 1 of 10

Question: At what site of the ribosome does tRNA bind to for translation elongation? _____

Answer: A site

Transcription/translation Flashcard 2 of 10

Question: In the final step of translation, a stop codon is recognized by _____ and the completed polypeptide is released from the ribosome

Answer:  factor

Transcription/translation Flashcard 3 of 10

Question: _____ ribosomes are unattached to any membrane and are the site of synthesis for cytosolic and organellar proteins

Answer: Free

Transcription/translation Flashcard 4 of 10

Question: In the first step of strand elongation, an _____ binds to the A site

Answer: aminoacyl-tRNA

Transcription/translation Flashcard 5 of 10

Question: While DNA polymerase binds to a primer, RNA polymerase binds to a _____

Answer: promoter

Transcription/translation Flashcard 6 of 10

Question: At what site of the ribosome does tRNA bind to for translation initiation? _____

Answer: P site

Transcription/translation Flashcard 7 of 10

Question: On the N terminal side of newly synthesized protein, a stretch of 10-15 hydrophobic amino acids forms the _____ sequence

Answer: N-terminal signal

Transcription/translation Flashcard 8 of 10

Question: The _____ ribosomal subunit initiates translation by binding to the 7-methylguanosine cap

Answer: 40s

Transcription/translation Flashcard 9 of 10

Question: Where does protein synthesis take place?

Answer: RER

Transcription/translation Flashcard 10 of 10

Question: ribosome

Answer: protein synthesis

Extra Information: 50S and 30S subunits