Question

If a splice site were mutated so that splicing did not take place, what would be the effect on the mRNA?

• A. It would be shorter than normal.
• B. It would be longer than normal.
• C. It would be the same length but would encode a different protein.
• D. The mRNA will be degraded.

Hint:

Splice site mutations are a common cause of human genetic diseases.
For example, mutations that cause intron retention or exon skipping disrupt the reading frame, leading to non-functional proteins.

Answer 1

The Correct Option is B

Step 1: Understanding the Concept:
In eukaryotic cells, genes contain coding regions called exons and non-coding regions called introns.
During transcription, the entire gene is transcribed into a precursor messenger RNA (pre-mRNA).
Splicing is the post-transcriptional modification process where introns are removed and exons are joined together by the spliceosome complex to produce a mature, functional mRNA.

Step 2: Detailed Explanation:
Splicing requires conserved consensus sequences at the intron-exon boundaries: a $5'$ donor splice site (typically GU), a $3'$ acceptor splice site (typically AG), and an internal branch point sequence.
These sequence elements are recognized by small nuclear ribonucleoprotein particles (snRNPs) that assemble the active spliceosome.
If a mutation occurs within one of these consensus splice sites (such as a point mutation at the conserved GU or AG dinucleotides), the spliceosome cannot recognize the boundary.
As a result, the splicing machinery cannot remove that intron, leading to intron retention.
Because the non-coding intron sequence remains within the final transcript, the mature mRNA will contain extra nucleotides.
This makes the resulting mRNA transcript longer than the normal, correctly spliced mRNA.
Intron retention often introduces a premature stop codon into the coding sequence, which can lead to a truncated, non-functional protein or trigger degradation via nonsense-mediated decay (NMD).
However, the physical length of the primary processed transcript remains longer than normal.

Step 3: Final Answer:
The retention of the unspliced intron causes the resulting mRNA to be longer than normal.