title: TOR regulates the subcellular distribution of DIM2, a KH domain protein required for cotranscriptional ribosome assembly and pre-40S ribosome export.
abstract: Eukaryotic ribosome synthesis is a highly dynamic process that involves the transient association of scores of trans-acting factors to nascent pre-ribosomes. Many ribosome synthesis factors are nucleocytoplasmic shuttling proteins that engage the assembly pathway at early nucleolar stages and escort pre-ribosomes to the nucleoplasm and/or the cytoplasm. Here, we report that two 40S ribosome synthesis factors, the KH-domain protein DIM2 and the HEAT-repeats/Armadillo-domain and export factor RRP12, are nucleolar restricted upon nutritional, osmotic, and oxidative stress. Nucleolar entrapment of DIM2 and RRP12 was triggered by rapamycin treatment and was under the strict control of the target of rapamycin (TOR) signaling cascade. DIM2 binds pre-rRNAs directly through its KH domain at the 5'-end of ITS1 (D-A(2) segment) and, consistent with its requirements in early nucleolar pre-rRNA processing, is required for efficient cotranscriptional ribosome assembly. The substitution of a single and highly conserved amino acid (G207A) within the KH motif is sufficient to inhibit pre-rRNA processing in a fashion similar to genetic depletion of DIM2. DIM2 carries an evolutionarily conserved putative nuclear export sequence (NES) at its carboxyl-terminal end that is required for efficient pre-40S ribosome export. Strikingly, DIM2 and RRP12 are both involved in the nucleocytoplasmic translocation of pre-ribosomes, suggesting that this step in the ribosome assembly pathway has been selected as a regulatory target for the TOR pathway.
authors.affiliation: Fonds de la Recherche Scientifique (FRS-FNRS), Académie Wallonie-Bruxelles, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Charleroi-Gosselies, B-6041, Belgium.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Vanrobays
authors.forename: Alexis
authors.initials: A
authors.lastname: Leplus
authors.forename: Yvonne N
authors.initials: YN
authors.lastname: Osheim
authors.forename: Ann L
authors.initials: AL
authors.lastname: Beyer
authors.forename: Ludivine
authors.initials: L
authors.lastname: Wacheul
authors.forename: Denis L J
authors.initials: DL
authors.lastname: Lafontaine