Alternative titles; symbols
HGNC Approved Gene Symbol: MRTO4
Cytogenetic location: 1p36.13 Genomic coordinates (GRCh38): 1:19,251,805-19,260,128 (from NCBI)
MRTO4 shuttles between the nucleus and cytoplasm and functions as a trans-acting factor in the maturation of pre-60S ribosomal subunits (Michalec et al. (2010)).
Using fluorescent-tagged proteins, Michalec et al. (2010) showed that human MRT4 predominantly localized to the nucleolus of transfected NIH3T3 cells, but that it also localized in the cytoplasm and associated with the ribosomal fraction. Human and yeast MRT4 both have a predicted N-terminal bipartite nuclear localization signal (NLS), but mutation analysis revealed that the predicted NLS was not absolutely required for MRT4 nuclear import and had only a minor influence on nuclear localization. Another short sequence in the N-terminal part of the protein also contributed to nuclear import of MRT4. Analysis with the yeast Mrt4 protein confirmed that nuclear localization of Mrt4 is conserved.
By gradient centrifugation, Rodriguez-Mateos et al. (2009) showed that the P0 (RPLP0; 180510) and Mrt4 proteins did not bind to the ribosome at the same time in yeast. Yeast P0 protein contains an N-terminal rRNA-binding domain that is homologous to the equivalent region of the Mrt4 protein. A chimeric protein in which the rRNA-binding site of P0 was substituted with the equivalent domain of Mrt4 partially complemented the absence of P0 in yeast and associated with ribosomes, although the association with ribosomes was weaker compared with wildtype P0. The results indicated that Mrt4 and P0 bind to the same region of rRNA and are therefore mutually exclusive in the ribosome. The predicted structure of the N-terminal domain of Mrt4 or P0 complexed with 25S rRNA provided further evidence that both proteins bind similarly to rRNA. These findings supported the hypothesis that Mrt4 binds first to pre-60S ribosomal particles, occupying the P0 site in the earlier assembly steps, and that it is then later displaced by the ribosomal protein.
Using a hybrid protein in which the rRNA-binding domain of yeast P0 was replaced by the equivalent domain from human MRT4, Michalec et al. (2010) showed that P0 and MRT4 have the same binding site on the ribosome. However, yeast and human MRT4 proteins are less closely related, P0 and MRT4 proteins localized to the different parts of the cells, and human MRT4 by itself did not support protein biosynthesis in yeast cells lacking P0 in complementation assays. Functional analysis with specific inhibitors revealed that nucleolar accumulation of MRT4 was rRNA-dependent, and that MRT4 was a trans-acting factor involved in ribosome maturation, with nucleus-cytoplasm shuttling capacity.
By mutation analysis, Michalec-Wawiorka et al. (2015) showed that the C terminus of human MRT4 determined its subcellular distribution in stress conditions. MRT4 contains 6 putative CK2 (see 115440) phosphorylation sites. Immunoprecipitation analysis confirmed that MRT4 was phosphorylated in human cells, and in vitro analysis showed that 3 C-terminal serine residues of MRT4 were phosphorylated by CK2. Further analysis indicated that equilibrium between MRT4 phosphorylation and dephosphorylation determined MRT4 behavior during nucleolar stress.
Gross (2023) mapped the MRTO4 gene to chromosome 1p36.13 based on an alignment of the MRTO4 sequence (GenBank BC006504) with the genomic sequence (GRCh38).
Gross, M. B. Personal Communication. Baltimore, Md. 8/15/2023.
Michalec, B., Krokowski, D., Grela, P., Wawiorka, L., Sawa-Makarska, J., Grankowski, N., Tchorzewski, M. Subcellular localization of ribosomal P0-like protein MRT4 is determined by its N-terminal domain. Int. J. Biochem. Cell Biol. 42: 736-748, 2010. [PubMed: 20083226] [Full Text: https://doi.org/10.1016/j.biocel.2010.01.011]
Michalec-Wawiorka, B., Wawiorka, L., Derylo, K., Krokowski, D., Boguszewska, A., Molestak, E., Szajwaj, M., Tchorzewski, M. Molecular behavior of human Mrt4 protein, MRTO4, in stress conditions is regulated by its C-terminal region. Int. J. Biochem. Cell Biol. 69: 233-240, 2015. [PubMed: 26494001] [Full Text: https://doi.org/10.1016/j.biocel.2015.10.018]
Rodriguez-Mateos, M., Abia, D., Garcia-Gomez, J. J., Morreale, A., de la Cruz, J., Santos, C., Remacha, M., Ballesta, J. P. The amino terminal domain from Mrt4 protein can functionally replace the RNA binding domain of the ribosomal P0 protein. Nucleic Acids Res. 37: 3514-3521, 2009. [PubMed: 19346338] [Full Text: https://doi.org/10.1093/nar/gkp209]