Biology
- Mrna Splicing
Genes of eukaryotic cells containing introns and exons. Introns, short for intervening sequences, are non-coding regions of a gene. They are transcribed but not translated into the amino acid sequence of proteins. Exons, or expressed sequences, are coding...
- Bypassing Involves Ribosome Movement
Certain sequences trigger a bypass event, when a ribosome stops translation, slides along mRNA with peptidyl-tRNA remaining in the P site, and then resumes translation (see Figure 7.30). This is a rather rare phenomenon, with only ~3 authenticated examples...
- Mrna Degradation Involves Multiple Activities
KEY CONCEPTS:Degradation of yeast mRNA requires removal of the 5 cap and the 3 poly(A). One yeast pathway involves exonucleolytic degradation from 5?3. Another yeast pathway uses a complex of several exonucleases that work in the 3?5 direction. The deadenylase...
- Bacterial Mrna Degradation Involves Multiple Enzymes
KEY TERMS:The degradosome is a complex of bacterial enzymes, including RNAase and helicase activities, which may be involved in degrading mRNA. KEY CONCEPTS: The overall direction of degradation of bacterial mRNA is 5?3. Degradation results from the...
- The 3 Terminus Is Polyadenylated
KEY TERMS:poly(A)+ mRNA is mRNA that has a 3 terminal stretch of poly(A). Poly(A) polymerase is the enzyme that adds the stretch of polyadenylic acid to the 3 of eukaryotic mRNA. It does not use a template. Poly(A)-binding protein (PABP) is the...
Biology
mRNA stability depends on its structure and sequence
KEY CONCEPTS:
- The modifications at both ends of mRNA protect it against degradation by exonucleases.
- Specific sequences within an mRNA may have stabilizing or destabilizing effects.
- Destabilization may be triggered by loss of poly(A)
The major features of mRNA that affect its stability are summarized in Figure 5.21. Both structure and sequence are important. The 5![]()
and 3![]()
terminal structures protect against degradation, and specific sequences within the mRNA may either serve as targets to trigger degradation or may protect against degradation:
- The modifications at the 5
and 3
ends of mRNA play an important role in preventing exonuclease attack. The cap prevents 5
?3
exonucleases from attacking the 5
end, and the poly(A) prevents 3
?5
exonucleases from attacking the 3
end.
- Specific sequence elements within the mRNA may stabilize or destabilize it. The most common location for destabilizing elements is within the 3
untranslated region. The presence of such an element shortens the lifetime of the mRNA.
- Within the coding region, mutations that create termination codons trigger a surveillance system that degrades the mRNA (see 5.14 Nonsense mutations trigger a surveillance system).
Destabilizing elements have been found in several yeast mRNAs, although as yet we do not see any common sequences or know how they destabilize the mRNA. They do not necessarily act directly (by providing targets for endonucleases), but may function indirectly, perhaps by encouraging deadenylation. The criterion for defining a destabilizing sequence element is that its introduction into a new mRNA may cause it to be degraded. The removal of an element from an mRNA does not necessarily stabilize it, suggesting that an individual mRNA can have more than one destabilizing element.
A common feature in some unstable mRNAs is the presence of an AU-rich sequence of ~50 bases (called the ARE) that is found in the 3![]()
trailer region. The consensus sequence in the ARE is the pentanucleotide AUUUA, repeated several times. Figure 5.22 shows that the ARE triggers destabilization by a two stage process: first the mRNA is deadenylated; then it decays. The deadenylation is probably needed because it causes loss of the poly(A)-binding protein, whose presence stabilizes the 3![]()
region (see 5.13 mRNA degradation involves multiple activities).
In some cases, an mRNA can be stabilized by specifically inhibiting the function of a destabilizing element. Transferrin mRNA contains a sequence called the IRE, which controls the response of the mRNA to changes in iron concentration. The IRE is located in the 3![]()
nontranslated region, and contains stem-loop structures that bind a protein whose affinity for the mRNA is controlled by iron. Figure 5.23 shows that binding of the protein to the IRE stabilizes the mRNA by inhibiting the function of (unidentified) destabilizing sequences in the vicinity. This is a general model for the stabilization of mRNA, that is, stability is conferred by inhibiting the function of destabilizing sequences (for review see Sachs, 1993; Ross, 1995).
- Mrna Splicing
Genes of eukaryotic cells containing introns and exons. Introns, short for intervening sequences, are non-coding regions of a gene. They are transcribed but not translated into the amino acid sequence of proteins. Exons, or expressed sequences, are coding...
- Bypassing Involves Ribosome Movement
Certain sequences trigger a bypass event, when a ribosome stops translation, slides along mRNA with peptidyl-tRNA remaining in the P site, and then resumes translation (see Figure 7.30). This is a rather rare phenomenon, with only ~3 authenticated examples...
- Mrna Degradation Involves Multiple Activities
KEY CONCEPTS:Degradation of yeast mRNA requires removal of the 5 cap and the 3 poly(A). One yeast pathway involves exonucleolytic degradation from 5?3. Another yeast pathway uses a complex of several exonucleases that work in the 3?5 direction. The deadenylase...
- Bacterial Mrna Degradation Involves Multiple Enzymes
KEY TERMS:The degradosome is a complex of bacterial enzymes, including RNAase and helicase activities, which may be involved in degrading mRNA. KEY CONCEPTS: The overall direction of degradation of bacterial mRNA is 5?3. Degradation results from the...
- The 3 Terminus Is Polyadenylated
KEY TERMS:poly(A)+ mRNA is mRNA that has a 3 terminal stretch of poly(A). Poly(A) polymerase is the enzyme that adds the stretch of polyadenylic acid to the 3 of eukaryotic mRNA. It does not use a template. Poly(A)-binding protein (PABP) is the...