Coupled GTPase and remodelling ATPase activities form a checkpoint for ribosome export

Article

关键词: NUCLEAR EXPORT;    SACCHAROMYCES-CEREVISIAE;    BIOGENESIS FACTORS;    ADAPTER PROTEIN;    RNA-BINDING;    MATURATION;    SUBUNIT;    ASSOCIATION;    COMPLEX;    KINASE;   

DOI  :  10.1038/nature12731

来源: SCIE

【 摘 要 】

Eukaryotic ribosomes are assembled by a complex pathway that extends from the nucleolus to the cytoplasm and is powered by many energy-consuming enzymes(1-3). Nuclear export is a key, irreversible step in pre-ribosome maturation(4-8), but mechanisms underlying the timely acquisition of export competence remain poorly understood. Here we show that a conserved Saccharomyces cerevisiae GTPase Nug2 (also known as Nog2, and as NGP-1, GNL2 or nucleostemin 2 in human(9)) has a key role in the timing of export competence. Nug2 binds the inter-subunit face of maturing, nucleoplasmic pre-60S particles, and the location clashes with the position of Nmd3, a key pre-60S export adaptor(10). Nug2 and Nmd3 are not present on the same pre-60S particles, with Nug2 binding before Nmd3. Depletion of Nug2 causes premature Nmd3 binding to the pre-60S particles, whereas mutations in the G-domain of Nug2 block Nmd3 recruitment, resulting in severe 60S export defects. Two pre-60S remodelling factors, the Rea1 ATPase and its co-substrate Rsa4, are present on Nug2-associated particles, and both show synthetic lethal interactions with nug2 mutants. Release of Nug2 from pre-60S particles requires both its K+-dependent GTPase activity and the remodelling ATPase activity of Rea1. We conclude that Nug2 is a regulatory GTPase that monitors pre-60S maturation, with release from its placeholder site linked to recruitment of the nuclear export machinery.

【 授权许可】

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