Based on the data, which of the following would be the most likely effect of a mutation that introduces a premature stop codon into a gene?

Core Concept

PILLAR 1 — MOLECULAR/CONCEPTUAL MECHANISM

Step-by-Step Analysis

A premature stop codon (also termed a nonsense mutation) arises when a single-base substitution in the coding DNA converts a sense codon into one of three termination signals—UAA, UAG, or UGA—within the open reading frame, upstream of the normal stop codon. During transcription, RNA polymerase II synthesizes a pre-mRNA that faithfully incorporates this aberrant termination triplet. After 5′-capping, intron removal via the spliceosome (comprising snRNPs U1, U2, U4/U6, and U5), and 3′ polyadenylation, the mature mRNA is exported through the nuclear pore complex to the cytoplasm for translation.

Why Other Options Are Wrong

When a ribosome initiates translation at the AUG start codon and proceeds through elongation, it will eventually encounter the premature stop codon in the A site. At this position, instead of an aminoacyl-tRNA pairing its anticodon with the mRNA codon through Watson-Crick hydrogen bonding, eukaryotic release factor eRF1 (or bacterial RF1/RF2) recognizes the stop codon and promotes hydrolysis of the ester bond linking the polypeptide to the tRNA in the P site. Translation terminates prematurely, releasing a truncated polypeptide that lacks the C-terminal amino acid sequence encoded downstream. This truncated protein is missing one or more structural domains—such as catalytic active sites, ligand-binding pockets, allosteric regulatory regions, or dimerization interfaces—rendering it incapable of performing its physiological function. In eukaryotes, the surveillance pathway nonsense-mediated mRNA decay (NMD) further recognizes these aberrant transcripts: if a stop codon is situated more than 50–55 nucleotides upstream of an exon–exon junction complex (EJC), proteins UPF1, UPF2, and UPF3 recruit decapping enzymes and exonucleases to degrade the mRNA, reducing transcript abundance.

PILLAR 2 — STEP-BY-STEP LOGIC

The question asks for the most likely effect of a premature stop codon. We must distinguish between the direct molecular consequence at the protein level and indirect effects on transcription or mRNA stability. The universal, organism-spanning outcome of a nonsense mutation is production of an incomplete polypeptide. Because three-dimensional protein conformation depends on the complete linear amino acid sequence folding into precise secondary structures (α-helices stabilized by backbone hydrogen bonds, β-sheets with inter-strand hydrogen bonds) and tertiary/quaternary interactions (hydrophobic collapse, disulfide bridges, ionic interactions), removal of even a modest C-terminal segment eliminates structural integrity. Enzymes lacking their catalytic residues, receptors missing transmembrane helices, or transcription factors devoid of DNA-binding domains cannot execute their cellular roles. Consequently, the protein product is nonfunctional—a conclusion independent of whether the mRNA escapes or is destroyed by NMD.

The phrase in the stimulus, 'most likely effect,' directs attention to this direct translational outcome rather than secondary regulatory phenomena, because every premature stop codon necessarily produces a truncated polypeptide, whereas mRNA degradation efficiency varies by organism, transcript, and cellular context.

PILLAR 3 — DISTRACTOR ANALYSIS

Option (A), 'Increased expression of the gene,' is incorrect because a premature stop codon exerts no mechanism to upregulate transcription. If anything, NMD decreases mRNA levels. Students selecting this option may conflate nonsense mutations with regulatory mutations in promoters or enhancers that increase transcription factor binding affinity—a fundamentally different molecular event.

Option (B), 'Decreased expression of the gene,' is an understandable trap. NMD does reduce transcript abundance in many eukaryotic scenarios, and bacterial ribosomes can stall and trigger mRNA degradation. However, 'gene expression' refers to the quantity of mRNA or protein produced, not the functionality of the product. The question asks for the most likely effect, and the definitive, universal consequence is a nonfunctional polypeptide—whether or not mRNA levels diminish. Selecting B reflects confusion between expression level and protein function.

Option (D), 'Increased stability of the protein,' contradicts established biochemistry. Truncated proteins generally exhibit reduced conformational stability because incomplete folding exposes hydrophobic amino acid residues (such as valine, leucine, and isoleucine) that are normally buried in the protein interior. This exposure marks the polypeptide for recognition by chaperones and ubiquitin ligases, targeting it for proteasomal destruction. Students drawn to D may mistakenly assume that a shorter polypeptide has fewer vulnerable sites, overlooking that proper folding—not chain length—governs protein half-life.