2 FUNCTIONALLY DISTINCT DOMAINS GENERATED BY IN-VIVO CLEAVAGE OF NUP145P - A NOVEL BIOGENESIS PATHWAY FOR NUCLEOPORINS

Nup145p is an essential yeast nucleoporin involved in nuclear export o f polyadenylated RNAs, We demonstrate here that Nup145p is cleaved in vivo to yield two functionally distinct domains: a carboxy-terminal do main (C-Nup145p) which is located at the nuclear pore complex (NPC) an d assembles into the Nup84p complex, and a GLFG-containing amino-termi nal domain (N-Nup145p) which is not part of this complex, Whereas the essential C-Nup145p accomplishes the functions required for efficient mRNA export and normal NPC distribution, N-Nup145p, which is homologou s to the GLFG-containing nucleoporins Nup100p and Nup116p, is not nece ssary for cell growth. However, the N-Nup145p becomes essential in a n up188 mutant background, Strikingly, generation of a free N-domain is a prerequisite for complementation of this peculiar synthetic lethal m utant, These data suggest that N- and C-domains of Nup145p perform ind ependent functions, and that the in vivo cleavage observed is of funct ional importance.