mRNA decay enzymes: Decap yeast and mammals

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

essenger RNA turnover is a critical exoribonuclease, XRN1 determinant of eukaryotic gene yeast, the deadenylatior expression. The stability of different capping pathway degrad mRNAs within the same cell can vary by rapidly than the exosome orders of magnitude and thus contribute pathway. The deadenyl greatly to differential expression levels. decapping pathway ane Moreover, the stability of individual mediated pathway apparn mRNAs can be regulated in response to a general decay mechanisr variety of stimuli, allowing for rapid alterconclusion is based on ations in gene expression. But how does that mRNAs are extrer eukaryotic mRNA turnover work, and both pathways are inacti how is it controlled? In this issue of PNAS, when both decay pathway Wang et al. (1) provide a piece to the the yeast cells die, which puzzle as to how eukaryotic mRNAs are critical importance of th degraded. of mRNA turnover for Early experiments in several eukaryotic and division. systems revealed that the 5' m7G cap and An unresolved issue ] the 3' poly(A) tail are critical protective mRNA decay enzymes a features of mRNAs. Work in the yeast common in eukaryotes ( Saccharomyces cerevisiae has uncovered yeast. Several lines of evid two general mRNA decay pathways that at least some aspects of tt act on these protective ends (Fig. 1; reconserved in eukaryotes. viewed in ref. 2). These pathways are tion precedes the decay of general in that they appear to degrade lian mRNAs in vivo, and p< most, if not all, normal mRNAs. The first that stimulate the step in both of these pathways is shortendecay of mammaing of the poly(A) tail (3-5), which can be lian mRNAs procatalyzed by one of two different enzymes. mote rapid deadThe major deadenylase appears to be a enylation (e.g., refs large l--mDa complex consisting of one 19 and 20). Second, known catalytic subunit, Ccr4p (6-8), a both the Ccr4p/ member of the ExoIII/AP endonuclease Pop2p/Not protein family (9), and several other proteins, complex (21-23 most notably, Pop2, Notl, Not2, Not3, and the Pan2p/ Not4, and NotS (10). Alternatively, a comPan3p deadenylase (24) plex of Pan2p/Pan3p can also function as eukaryotic genomes. M a cytoplasmic deadenylase (6, 11, 12). Ccr4p, like yeast Ccr4p, 1 Deadenylation of the 3' tail to a length nuclease domain in its C that is too short to bind the major poly(A)function as a deadenylas( binding protein, Pabpl, can lead to two additional poly(A) ribonu consequences in yeast. First, it can leave present in vertebrates (25, the 3' end susceptible to a complex of ing to note that the three c multiple 3'-5' exonucleases called the exodistinct substrate specific some (5, 13). Alternatively, loss of Pabpl Pop2/Not complex and I is thought to bring about a transition in the ited by Pablp in vitro (8, structure of the proteins associated with Pan2p/Pan3p complex re the mRNA, the mRNP, that disposes the activity (11-12). In additic 5' end of the mRNA to decapping (14, 15). ulated by the presence of Decapping requires two proteins, Dcplp (27), whereas CCR4 is and Dcp2p, that physically associate with These differences in specil each other (16, 17). Removal of the 5' in vivo, mRNAs with diffe] protective cap leaves the mRNA subject to tures may be preferentiall1 5'-3' exonucleolytic degradation by the alternative deadenylases,