Disease relevance of GLE2

• We found that an mRNA export factor Gle2p rapidly dissociated from the nuclear envelope and diffused into the cytoplasm at 42 degrees C. However, in exponential phase cells pretreated with mild heat stress (37 degrees C for 1 h), Gle2p did not dissociate at 42 degrees C, and the export of bulk poly(A)(+) mRNA continued [1].

High impact information on GLE2

• Gle2p is anchored at the nuclear envelope (NE) via a short Gle2p-binding motif within Nup116p called GLEBS [2].
• Gle2p is implicated in nuclear export of poly(A)+ RNA and nuclear pore complex (NPC) structure and distribution in Saccharomyces cerevisiae [2].
• Nup116p and nup100p are interchangeable through a conserved motif which constitutes a docking site for the mRNA transport factor gle2p [3].
• Using the GFP-Nup49p system with a mutant in the NPC-associated factor Gle2p that exhibits formation of NPC clusters only at 37 degrees C, it was possible to distinguish between these two models for NPC dynamics [4].
• The dissociation of Gle2p was caused by increased membrane fluidity and correlated closely with blocking of the export of bulk poly(A)(+) mRNA [1].

Biological context of GLE2

• The mRNA export factor RAE1 (also called GLE2) and the mitotic checkpoint protein BUB3 share extensive sequence homology in yeast as well as higher eukaryotes, although the biological relevance of their similarity is unclear [5].
• The progeroid phenotypes caused by deficiency of Bub3 and Rae1 are tightly linked to precocious activation of cellular senescence, but not apoptotic, programs [6].

Anatomical context of GLE2

• When the GLEBS is deleted from Nup116p, Gle2p dissociates from the nuclear envelope and clusters of herniated nuclear pores form [3].

Physical interactions of GLE2

• Thus, the in vivo function of Gle2p is strictly coupled to the short GLEBS within Nup116p which links this putative mRNA transport factor to the nuclear pores [3].
• A ptr1-1 rae1-167 double mutant showed a synthetic effect on a growth defect, indicating that Ptr1p functionally interacts with an essential mRNA export factor Rae1p [7].

Other interactions of GLE2

• Gle2p physically associated with Nup116p in vitro, and the interaction required the N-terminal region of Nup116p [8].
• By fluorescence-activated cell sorting for cells with low GFP signal from a population of mutagenized cells expressing GFP-Nup49p, three complementation groups were identified: two correspond to mutant nup120 and gle2 alleles that result in clusters of NPCs [9].
• With regard to genetic specificity, the nup116-C lethality was also suppressed by high-copy GLE2 and NIC96 [8].
• Interestingly, a two-hybrid interaction was detected between Gle2p and Srp1p, the nuclear localization signal receptor, as well as Rip1p, a nuclear export signal-interacting protein [10].
• Comparison of the Bub3 sequence to the WD40 protein, Rae1, shows high sequence conservation along the same surfaces [11].

Analytical, diagnostic and therapeutic context of GLE2

• In indirect immunofluorescence and nuclear pore complex fractionation experiments, Gle2p was associated with nuclear pore complexes [10].
• Immunofluorescence and thin-section electron microscopic analysis revealed that the nuclear pore complex and nuclear envelope structure was grossly perturbed in gle2 mutants [10].

References