Most mRNAs in a bacterial cell are very unstable, having half-lives of less than a couple of minutes. Exonucleases, which degrade in the 3ʹ-to-5ʹ direction, are usually responsible for the rapid destruction of these mRNAs. Because its mRNAs are both rapidly synthesized and rapidly degraded, a bacterium can adapt quickly to environmental changes.
As a general rule, the mRNAs in eukaryotic cells are more stable. Some, such as that encoding β globin, have half-lives of more than 10 hours, but most have considerably shorter half-lives, typically less than 30 minutes. The mRNAs that code for proteins such as growth factors and transcription regulators, whose production rates need to change rapidly in cells, have especially short half-lives.
We saw in Chapter 6 that the cell has several mechanisms that rapidly destroy incorrectly processed RNAs; here, we consider the fate of the typical “normal” eukaryotic mRNA. Two general mechanisms exist for eventually destroying each mRNA that is made by the cell. Both begin with the gradual shortening of the poly-A tail by an exonuclease, a process that starts as soon as the mRNA reaches the cytosol. In a broad sense, this poly-A shortening acts as a timer that counts down the lifetime of each mRNA. Once the poly-A tail is reduced to a critical length (about 25 nucleotides in humans), the two pathways diverge. In one, the 5ʹ cap is removed (a process called decapping) and the “exposed” mRNA is rapidly degraded from its 5ʹ end. In the other, the mRNA continues to be degraded from the 3ʹ end, through the poly-A tail, into the coding sequences (Figure 7–69).
Nearly all mRNAs are subject to both types of decay, and the specific sequences of each mRNA determine how fast each step occurs and therefore how long each mRNA will persist in the cell and be able to produce protein. The 3ʹ UTR sequences are especially important in controlling mRNA lifetimes, and they often carry binding sites for specific proteins that increase or decrease the rate of poly-A shortening, decapping, or 3ʹ-to-5ʹ degradation. The half-life of an mRNA is also affected by how efficiently it is translated. Poly-A shortening and decapping compete directly with the machinery that translates the mRNA; therefore, any factors that affect the translation efficiency of an mRNA will tend to have the opposite effect on its degradation (Figure 7–70).
Although poly-A shortening controls the half-life of most eukaryotic mRNAs, some mRNAs can be degraded by a specialized mechanism that bypasses this step altogether. In these cases, specific nucleases cleave the mRNA internally,
Figure 7–69 Two mechanisms of eukaryotic mRNA decay. A critical threshold of poly-A tail length induces rapid 3ʹ-to-5ʹ degradation, which may be triggered by the loss of the poly-Abinding proteins. As shown in figure 7–70, a deadenylase associates with both the 3ʹ poly-A tail and the 5ʹ cap, and this connection may be involved in signaling decapping after poly-A shortening. Although 5ʹ-to-3ʹ and 3ʹ-to-5ʹ degradation are shown here on separate rnA molecules, these two processes can occur together on the same molecule. (Adapted from C.A. Beelman and r. parker, Cell 81:179–183, 1995. with permission from elsevier.)