| 2009 |
Yvh1 (dual-specificity phosphatase) is required for the release of Mrt4 from pre-60S subunits in the cytoplasm; deletion of YVH1 causes Mrt4 to persist on cytoplasmic pre-60S subunits. A mutation in Mrt4 at the protein-RNA interface (G68D) bypasses the requirement for Yvh1, indicating Yvh1 acts by disrupting the Mrt4-rRNA interaction. Pre-60S subunits associated with Yvh1 contain Rpl12 but lack both Mrt4 and P0, suggesting a linear assembly order: Yvh1 binds pre-60S to displace Mrt4, then P0 loads to assemble the mature stalk, then Yvh1 is released. |
Genetic deletion/mutation analysis, sucrose gradient fractionation, co-immunoprecipitation, suppressor mutation mapping (Mrt4-G68D bypasses Yvh1 requirement) |
The Journal of cell biology |
High |
19797078
|
| 2009 |
Mrt4 and P0 compete for binding to the same site (the 25S rRNA GAR domain) on the large ribosomal subunit and cannot bind simultaneously. Mrt4 defines medium pre-60S particles in the nucleus/nucleoplasm, while P0 is found only in late/cytoplasmic pre-60S complexes. Loss of Mrt4 causes P0 to assemble prematurely onto nuclear (medium) pre-60S particles; loss of P0 causes Mrt4 to relocate to the cytoplasm within aberrant 60S subunits. Thus Mrt4 controls the timing and position of P0 assembly, and P0 is required for Mrt4 release. |
TAP-tag purification, sucrose gradient sedimentation, fluorescence microscopy, genetic depletion (conditional null mutants) |
Nucleic acids research |
High |
19789271
|
| 2009 |
Mrt4 and P0 bind to the same site on the 25S rRNA. A chimera containing the N-terminal 137 amino acids of Mrt4 fused to the C-terminal 190 amino acids of P0 can partially complement a P0 null mutant and associates with ribosomes, though with weaker binding than wild-type P0. Ribosomes bearing the chimera contain less P1/P2 and show altered L12 interaction, indicating that the N-terminal domain of Mrt4 directs rRNA binding while differences in the C-terminal region affect stalk protein interactions. |
Chimeric protein complementation assay, ribosome co-sedimentation, molecular dynamics simulation, yeast genetics |
Nucleic acids research |
Medium |
19346338
|
| 1999 |
Temperature-sensitive mutation in MRT4 causes defects in mRNA decay of several mRNAs without impairing protein synthesis, identifying Mrt4 as a factor with a role in mRNA turnover independent of general translation. |
Genetic complementation, mRNA decay assays (Northern blot/pulse-chase), temperature-sensitive mutant characterization |
Genetics |
Medium |
10471698
|
| 2010 |
Human MRTO4 (hMrt4) localizes predominantly to the nucleolar compartment (unlike cytoplasmic P0/P1/P2) and binds to the same site on the large ribosomal subunit as P0 but cannot functionally replace P0. Nucleolar accumulation of hMrt4 depends on interaction with rRNA rather than a specific nucleolus-targeting signal, while nuclear import requires a short sequence in the N-terminal domain. Treatment with actinomycin D or leptomycin B confirmed nucleus-cytoplasm shuttling capacity and trans-acting role in ribosome maturation. |
Fluorescence microscopy, biochemical fractionation, inhibitor treatments (actinomycin D, leptomycin B), chimeric protein domain-swap analysis |
The international journal of biochemistry & cell biology |
Medium |
20083226
|
| 2015 |
Human MRTO4 undergoes phosphorylation in vivo; serines S229, S233, and S235 within its acidic C-terminal extension are phosphorylated by CK2 kinase in vitro. This phosphorylation does not alter the subcellular distribution of hMrt4 under normal conditions but affects its molecular behavior during actinomycin D-induced nucleolar stress, identifying the C-terminal region as a regulatory element linking ribosome biogenesis to the stress response pathway. |
In vivo phosphorylation assay, in vitro kinase assay (CK2), site-directed mutagenesis of S229/S233/S235, fluorescence microscopy under stress conditions |
The international journal of biochemistry & cell biology |
Medium |
26494001
|
| 2011 |
Genetic interaction between Yvh1 and Mrt4 is essential for normal glycogen accumulation, mRNA decay, and induction of early meiotic genes (IME2, SPO13, HOP1). The Mrt4(G68D) suppressor allele (mutation at the rRNA-binding interface) restores all of these Yvh1-deletion phenotypes, indicating they are downstream consequences of the Yvh1-Mrt4 ribosome assembly axis rather than separate Yvh1 functions. |
Genetic suppressor analysis, mRNA decay assays, glycogen accumulation assay, sporulation gene expression analysis, dominant suppressor screen |
Journal of biochemistry |
Medium |
21474464
|
| 2024 |
MRTO4 promotes glycolysis in hepatocellular carcinoma cells and accelerates HCC progression by inhibiting the glycolytic enzyme ALDOB. Knockdown of MRTO4 reduced glycolysis, proliferation, and invasion while promoting apoptosis; this mechanism was attributed to MRTO4-mediated suppression of ALDOB. |
RT-qPCR, Western blotting, CCK8, TUNEL, clone formation assay, Transwell assay, ELISA, immunohistochemistry, siRNA knockdown |
Medical science monitor |
Low |
38778508
|
| 2026 |
Mrt4 binds rRNA through cysteines C96 and C189 on Candida albicans Mrt4 (CaMrt4); covalent engagement of both residues by a fumaramidmycin-derived compound selectively inhibits CaMrt4-rRNA interaction and disrupts fungal ribosomal assembly. Human MRTO4-rRNA interaction is not inhibited by this compound, establishing a structural/mechanistic distinction between fungal and human Mrt4 at the rRNA-binding interface. |
Activity- and inactive-based protein profiling (AIBPP), chemical-genetic profiling, fluorescence polarization assay, in vivo Galleria mellonella and murine candidiasis models |
Nature communications |
Medium |
41781388
|