Gene Control Through RNA Stability

The amount of a protein that is synthesized depends on the amount of corresponding mRNA available for translation. The amount of available mRNA, in turn, depends on both the rate of mRNA synthesis and the rate of mRNA degradation. Eukaryotic mRNAs are generally more stable than bacterial mRNAs, which typically last only a few minutes before being degraded, but nonetheless there is great variability in the stability of eukaryotic mRNA: some persist for only a few minutes; others last for hours, days, or even months. These variations can result in large differences in the amount of protein that is synthesized.

Cellular RNA is degraded by ribonucleases, enzymes that specifically break down RNA. Most eukaryotic cells contain 10 or more types of ribonucleases, and there are several different pathways of mRNA degradation. In one pathway, the 5' cap is first removed, followed by 5': 3'

removal of nucleotides. A second pathway begins at the 3' end of the mRNA and removes nucleotides in the 3': 5' direction. In a third pathway, the mRNA can be cleaved at internal sites.

Messenger RNA degradation from the 5' end is most common and begins with the removal of the 5' cap. This pathway is usually preceded by the shortening of the poly(A) tail. Poly(A)-binding proteins (PABPs) normally bind to the poly(A) tail and contribute to its stability-enhancing effect. The presence of these proteins at the 3' end of the mRNA protects the 5' cap. When the poly(A) tail has been shortened below a critical limit, the 5' cap is removed, and nucle-ases then degrade the mRNA by removing nucleotides from the 5' end. These observations suggest that the 5' cap and 3' poly(A) tail of eukaryotic mRNA physically interact with each other, most likely by the poly(A) tail bending around so that the PABPs make contact with the 5' cap (see Chapter 14). Other parts of eukaryotic mRNA, including sequences in the 5' UTR, the coding region, and the 3' UTR, also affect mRNA stability.

Poly(A) tails are added to the 3' ends of some bacterial mRNAs, but they are shorter than those typically associated with eukaryotic mRNA and have the opposite effect; they appear to destabilize most prokaryotic mRNAs.

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