RNA splicing removes introns from pre-mRNA via a two-step transesterification reaction. In the first step, the 2'-OH of the branch point adenosine attacks the 5' splice site, forming a lariat intermediate. Mutations in the invariant GU dinucleotide at the 5' splice site would MOST likely result in:
- A Intron retention or aberrant splice site use, potentially introducing premature stop codons or frameshifts ✓
- B Efficient exon skipping with production of a shorter but functional protein
- C Enhanced spliceosome assembly due to stronger U1 snRNA binding
- D Increased polyadenylation efficiency at the 3' end of the mRNA
Correct answer: A. Intron retention or aberrant splice site use, potentially introducing premature stop codons or frameshifts
Explanation
The 5' splice site consensus sequence (GU) is recognized by U1 snRNA base pairing; mutation of the invariant GU abolishes this recognition. The consequences include intron retention (entire intron remains in the mRNA), use of cryptic splice sites (leading to frameshifts or exon skipping), or nonsense-mediated mRNA decay if a premature stop codon is introduced. Such splice site mutations account for approximately 10-15% of all disease-causing mutations — for example, beta-thalassemia type I is commonly caused by 5' splice site mutations in the beta-globin gene.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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