A missense mutation changes the 5' splice donor site (GT→AT) of an exon-intron junction in a gene. Which consequence on the mRNA is most likely?

• A Polyadenylation at an alternative site producing a shorter mRNA
• B RNA polymerase II stalls and degrades the RNA before the mutation site
• C Exon skipping or intron retention, producing aberrant protein or premature stop codon ✓
• D The ribosome skips the mutated codon, producing a frameshifted protein from the downstream exon

Explanation

The 5' splice donor site consensus is GU (RNA), and the GT→AT mutation abolishes the obligatory GU required for U1 snRNA recognition during spliceosome assembly. Without a functional donor site, the spliceosome either skips the upstream exon (exon skipping) or fails to remove the intron (intron retention). Intron retention introduces intronic sequence into the mRNA, typically causing a frameshift or premature stop codon → nonsense-mediated decay or truncated protein. This mechanism underlies many cases of beta-thalassemia (IVS1-1 G>A, IVS1-6 T>C mutations).

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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