D2.2.3 Control of the degradation of mRNA Notes

mRNA Degradation Ensures Proteins Are Produced in The Correct Amounts and At The Right Time

1. This process is tightly regulated to control how long an mRNA molecule remains active in the cell.
2. This mechanism allows cells to adapt protein synthesis to their immediate needs, ensuring efficiency and precision in response to internal and external cues.

The Timing of mRNA Degradation is Very Important

1. The lifespan of mRNA molecules plays a critical role in regulating protein production.
2. Some mRNAs persist only for minutes to allow rapid changes in protein levels, while others last for days to ensure sustained protein synthesis.
3. This controlled degradation enables the cell to:
   1. Regulate Protein Production: Quickly degrade mRNA for proteins that are no longer needed, preventing overproduction.
   2. Adapt to Environmental Changes: Degrade mRNA rapidly in response to changing conditions, such as stress or nutrient availability.
   3. Conserve Energy: Stop unnecessary protein synthesis to save cellular resources.

Key Mechanisms of mRNA Stability and Degradation

1. Poly-A Tail is A Timer for mRNA Lifespan

1. After transcription, a poly-A tail (a sequence of adenine nucleotides) is added to the 3′ end of the mRNA.
2. The poly-A tail serves as a protective barrier against degradation, but over time, it is gradually shortened by enzymes called deadenylases.
   1. When the poly-A tail becomes too short, the mRNA is marked for degradation.
   2. The length of the poly-A tail helps determine whether an mRNA persists for minutes or days, acting like a "timer" for its lifespan.

2. Decapping and Exonuclease Activity

1. Once the poly-A tail is shortened, the 5′ cap of the mRNA is removed in a process called decapping.
2. This exposes the mRNA to nucleases, which break it down from both ends:
   1. 5′ to 3′ Exonuclease: Degrades the mRNA from the exposed 5′ end.
   2. 3′ to 5′ Exosome Complex: Breaks down the remaining RNA from the 3′ end.

Examples of mRNA Lifespan in Action

1. Short-Lived mRNAs (Minutes): Encode proteins for rapid, transient responses, such as those involved in signalling pathways.
2. Long-Lived mRNAs (Days): Encode proteins needed for sustained cellular functions, such as structural components or enzymes.