Question

Predict the likely effects of a mutation in the sequence \(\left(5^{\prime}\right)\) AAUAAA in a eukaryotic mRNA transcript.

Short answer

A mutation in the AAUAAA sequence can impair polyadenylation, leading to unstable mRNA and reduced protein synthesis.

Step-by-step solution

Understanding the Function of the Sequence

The sequence \( AAUAAA \) is a polyadenylation signal located in the 3'-untranslated region (3'-UTR) of a eukaryotic mRNA. It signals the cellular machinery to cleave the mRNA transcript at a site downstream and add a poly-A tail. This poly-A tail is important for mRNA stability, nuclear export, and translation initiation.

Identifying Mutation Impact on Polyadenylation

If a mutation occurs in the \( AAUAAA \) sequence, polyadenylation may be impaired because the cellular machinery may not recognize the mutated sequence efficiently. This can lead to the mRNA being cleaved at incorrect sites, or not cleaved at all, resulting in transcripts without a proper poly-A tail.

Predicting Effects on mRNA Stability and Translation

Without a poly-A tail, the mRNA transcript is unstable and may be rapidly degraded in the cell. This degradation reduces the amount available for translation, potentially decreasing protein synthesis from that transcript. Additionally, if mRNA is not efficiently exported from the nucleus to the cytoplasm, translation could be further hindered.

Overall Impact Assessment

The mutation in the \( AAUAAA \) sequence could lead to reduced gene expression of the mRNA's encoded protein. This reduction could affect cellular processes or pathways that rely on that protein, potentially causing varying effects depending on the protein's function.

Key concepts

mRNA Stability

Messenger RNA (mRNA) stability is crucial for proper gene expression and cellular function. It determines how long an mRNA molecule remains intact in a cell, thus affecting the amount of protein that can be produced from it. The poly-A tail, a chain of adenine nucleotides added to the end of an mRNA molecule, plays a significant role in maintaining mRNA stability.

The poly-A tail protects the mRNA from enzymatic degradation. Enzymes that typically break down RNA molecules find it difficult to attack an mRNA with a strong poly-A tail, allowing it to be translated into protein multiple times.

Aside from preventing degradation, the tail also aids in the efficient translation of mRNA into protein. It interacts with specific proteins to form a "closed loop" structure, enhancing the initiation of translation. If the poly-A tail is incomplete or missing, mRNA stability decreases, leading to rapid degradation and reduced protein synthesis.

3'-Untranslated Region

The 3'-untranslated region (3'-UTR) is an important section of an mRNA transcript following the coding sequence. While it does not code for a protein, it plays several vital roles in regulating mRNA stability and translation.

Within the 3'-UTR lies the polyadenylation signal, typically the sequence \( AAUAAA \), crucial for the subsequent addition of the poly-A tail. This region helps determine how long the mRNA stays within the cell, influencing gene expression levels.

The 3'-UTR can also contain various regulatory elements such as binding sites for proteins and microRNAs. These elements can either stabilize the mRNA, helping it produce protein for longer periods, or target it for degradation, quickly reducing protein levels.

• Contains polyadenylation signals
• Influences mRNA stability
• Holds regulatory elements

Understanding the 3'-UTR's roles is essential to comprehend how mRNA behavior impacts overall gene expression.

Mutation Impact on Gene Expression

Mutations can significantly alter gene expression by affecting the mRNA sequence and its subsequent processing. When mutations occur in critical regions such as the polyadenylation signal \( AAUAAA \), they might disrupt normal cellular processes.

If the signal is mutated, polyadenylation may be impaired. This impairment can lead to incorrect mRNA cleavage sites or the absence of proper poly-A tails, resulting in unstable mRNA. Such mRNA is more prone to degradation and might not reach the cytoplasm efficiently.

This instability decreases the availability of the mRNA for translation, subsequently reducing the amount of protein produced. Therefore, mutations impacting sequences like \( AAUAAA \) directly affect mRNA stability and gene expression.

Such disruptions can have significant biological consequences, depending on the function of the affected protein. In some cases, they may lead to diseases or developmental issues if the protein plays a critical role in cellular pathways.