Diauxic shift-dependent relocalization of decapping activators Dhh1 and Pat1 to polysomal complexes

Drummond, Sheona P.; Hildyard, John; Firczuk, Helena; Reamtong, Onrapak; Li, Ning; Kannambath, Shichina; Claydon, Amy J.; Beynon, Robert J.; Eyers, Claire E.; McCarthy, John E. G.

Two proteins, Dhh1 and Pat1, are thought to lie at the heart of the relationship between translation and mRNA degradation (4) . Dhh1 and Pat1 act as activators of decapping and, at least under conditions of overexpression, they are capable of repressing translation in vivo (4) . However, other results suggest that Pat1 (at normal cellular levels) acts to promote translation initiation at a step before or during 40S ribosomal recruitment onto mRNA (5) . In other eukaryotes, such as Xenopus and Drosophila, Dhh1 orthologues have been shown to be involved in translational repression of specific mRNAs during early development (6, 7) . It has previously been postulated that translational repression generically drives mRNAs into P *To whom correspondence should be addressed. Tel. [phone]; Fax: [phone]; Email: bodies (and thus accelerated decay), and that translational repression is in constant competition with active translation (4) . Other reports have suggested that the decay rate may be modulated differentially in response to distinct types of translational control event and that translationdecay relationships can be mRNA species specific (8, 9) . While mRNA decapping, which plays a key role in mRNA degradation (4) , can be inhibited by the capbinding protein eIF4E in vitro and in vivo (1, 2, 10, 11) , it is neither clear how this apparently competitive relationship is controlled nor at what stage it features in modulating the balance between translation and decay. Very recent work has also shifted the emphasis of current thinking by revealing that, as in bacteria (9, 12, 13) , mRNA decay in Saccharomyces cerevisiae can be co-translational (14) although this does not rule out the possibility that translation and decay mutually influence or regulate each other. Against this complex background of previous findings, it is important to know how Dhh1 and Pat1 participate in controlling the relationship between the translation apparatus and the decay machinery.