The T-cell leukemia related rpl10-R98S mutant traps the 60S export adapter Nmd3 in the ribosomal P site in yeast.

ABSTRACT: Mutations in the ribosomal protein Rpl10 (uL16) can be drivers of T-cell acute lymphoblastic leukemia (T-ALL). We previously showed that these T-ALL mutations disrupt late cytoplasmic maturation of the 60S ribosomal subunit, blocking the release of the trans-acting factors Nmd3 and Tif6 in S. cerevisiae. Consequently, these mutant ribosomes do not efficiently pass the cytoplasmic quality control checkpoint and are blocked from engaging in translation. Here, we characterize suppressing mutations of the T-ALL-related rpl10-R98S mutant that bypass this block and show that the molecular defect of rpl10-R98S is a failure to release Nmd3 from the P site. Suppressing mutations were identified in Nmd3 and Tif6 that disrupted interactions between Nmd3 and the ribosome, or between Nmd3 and Tif6. Usi

SUBMITTER: Patchett S 

PROVIDER: S-EPMC5536393 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature