mRNA-stabiliteit en genexpressie

The extent and timing of gene expression is affected by mRNA stability.

Stable mRNAs can have half-lives of several hours and encode proteins that need to be continuously produced. Protein synthesis can continue long after transcription stops if an mRNA is not degraded.

In contrast, unstable mRNAs usually have short half-lives of less than 30 minutes and are rapidly degraded.  Unless transcription of these genes is continuous, the mRNA can only be only translated for a short time. This helps an organism to quickly stop producing unnecessary proteins.

mRNAs are degraded by three different pathways.

The most common method is the deadenylation dependent pathway, where adenines are removed from the poly-A tail of an mRNA, triggering its degradation from both ends of the transcript.

The deadenylating nuclease complex degrades the poly-A tail in a 3’ to 5’ direction. After the adenines are removed, the mRNA is further degraded in the same direction by the cytoplasmic exosome complex.

The 5’ end of an mRNA has a cap to protect it from exonucleases. The mRNA often forms a loop where its 5’ cap and 3’ poly-A tail are held closely together by specific proteins. 

When the poly-A tail gets reduced to less than 15 residues, many of these proteins cannot bind to the poly-A tail which exposes the 5’ cap to the decapping enzymes.  This subsequently results in the decapping of the 5’ end. 

This decapped mRNA is then degraded from 5’ to 3’ direction by another exonuclease. 

The second type of degradation is a deadenylation independent pathway where decapping enzymes remove the 5’ caps. An exonuclease then degrades the unprotected mRNA from the 5’ to 3’ end.

The third and least frequent pathway involves the internal cleavage of an mRNA using specific endonucleases. The fragments of the mRNA have unprotected 5’ and 3’ ends. Specific exonucleases then can act on these unprotected ends and degrade the mRNA.

The degradation of mRNA occurs in aggregated protein bodies known as processing, or P bodies. These P bodies contain enzymes including those involved in decapping and the 5’ to 3’ degradation of the mRNA.