9. Yeast mRNA degradation involves multiple activities

5.9 Yeast mRNA degradation involves multiple activities

Key terms defined in this section

Exosome is a complex of several exonucleases involved in degrading RNA.

Figure 5.21 Degradation of yeast mRNA requires deadenylation, decapping, and exonucleolysis.

The pathway for degradation of mRNA is different in yeast. Figure 5.21 shows that the modifications at each end of the mRNA provide an obstacle to degradation. They must be removed in a specific order. First the mRNA is deadenylated, leaving it with a short stretch of poly(A). The mechanism is not known, but is usually pictured in terms of an exonucleolytic activity. Removal of the poly(A) is necessary for a decapping enzyme to cleave off the methylated cap. The basis for this relationship is that the presence of the PABP (poly(A)-binding protein) on the poly(A) prevents the decapping enzyme from binding to the 5′ end. PABP is released when the length of poly(A) falls below 10 V15 residues. The decapping reaction occurs by cleavage 1 V2 bases from the 5′ end.

The effect of PABP on decapping implies a relationship between events occurring at the two ends of the mRNA It is possible that the 5′ and 3′ ends in fact are connected in the ribonucleoprotein particle. Once the cap has been removed, the mRNA is degraded rapidly from the 5′ end, by the 5′ V3′ exonuclease XRN1.

Deadenylated mRNAs also can be degraded by the 3′ V5′ exonuclease activity of the exosome, a complex of >5 exonucleases. The exosome is also involved in processing precursors for rRNAs. The aggregation of the individual exonucleases into the exosome complex may enable 3′ V5′ exonucleolytic activities to be coordinately controlled. Yeast mutants lacking either exonucleolytic pathway degrade their mRNAs more slowly, but the loss of both pathways is lethal (426; for review see 30).

Reviews
30:	Jacobson, A. and Peltz, S. W. (1996). Interrelationships of the pathways of mRNA decay and translation in eukaryotic cells. Ann. Rev. Biochem 65, 693-739.

Research
426:	Mitchell, P. et al. (1997). The exosome: a conserved eukaryotic RNA processing complex containing multiple 3?/FONT>-5?/FONT> exoribonuclease activities. Cell 91, 457-466.