GRC5 and NMD3 function in translational control of gene expression and interact genetically

Abstract

The yeast gene, GRC5 (growth control), is a member of the highly conserved QM gene family, the human member of which has been associated with the suppression of Wilms' tumor. GRC5 encodes ribosomal protein L10, which is thought to play a regulatory role in the translational control of gene expression. A revertant screen identified four spontaneous revertants of the mutant grc5-1ts allele. Genetic and phenotypic analysis showed that these represent one gene, NMD3, and that the interaction of NMD3 and GRC5 is gene-specific. NMD3 was previously identified as a component of the nonsense-mediated mRNA decay pathway. The point mutations within NMD3 reported here may define a domain important for the functional interaction of Grc5p and Nmd3p.

Nuclear Export of 60S Ribosomal Subunits Depends on Xpo1p and Requires a Nuclear Export Sequence-Containing Factor, Nmd3p, That Associates with the Large Subunit Protein Rpl10p

“…Previous work showed that the two nonribosomal proteins Nmd3p and Rsa1p are genetically linked to Rpl10p (16,17). Rsa1p is a nuclear protein implicated in facilitating the association of Rpl10p with the 60S ribosomal subunits (17).…”

“…This gene encodes the ribosomal protein Rpl10p (21), which was reported to assemble late with 60S subunits. Since Rpl10p was reported to interact with Nmd3p, a nonribosomal protein that associates with 60S subunits (3,12,13,16), we analyzed whether Nmd3p plays a role in nuclear export of ribosomes. We find that nmd3 ts mutants accumulate the large subunit reporter Rpl25-eGFP inside the nucleus at the restrictive temperature.…”

Mapping the Functional Domains of Yeast NMD3, the Nuclear Export Adapter for the 60 S Ribosomal Subunit

“…The second region (approximately aa 290 -380) spans the region in which suppressor mutations were identified previously (Fig. 7A) (17). The strongest suppressor, I112T,I362T, contained two mutations, one in each domain.…”

“…Mutations in NMD3 That Suppress rpl10 Mutants-Three spontaneous nmd3 mutants (I279F, L291F, and A336P) were previously identified as suppressors of the temperature-sensitive rpl10[G161D] allele of the large ribosomal subunit protein Rpl10p (17). To understand the genetic interaction of Nmd3p with Rpl10p more completely, we screened for additional NMD3 suppressors.…”

QM, a Putative Tumor Suppressor, Regulates Proto-oncogene c-Yes

“…In contrast, another study contended that QM was associated with presenilin 1 (PS1) and translocates from cytoplasm to nucleus resulting in suppression of the complex formation of the c-Jun homodimer (20). In another report, it has been demonstrated that yeast QM homologous genes, such as GRC5 and QSR1, participate in translational control of gene expression in yeast (21). These are especially required for cell growth and differentiation throughout mRNA translation, because they take part in the recombination of 60 and 40 S ribosomal protein subunits.…”