Alternative titles; symbols
HGNC Approved Gene Symbol: TRNAU1AP
Cytogenetic location: 1p35.3 Genomic coordinates (GRCh38): 1:28,553,085-28,578,545 (from NCBI)
TRNAU1AP binds selenocysteine tRNA (tRNA-sec; see 165060) and is a component of the selenocysteine biosynthesis pathway (Ding and Grabowski, 1999; Oudouhou et al., 2017).
Ding and Grabowski (1999) cloned rat Trnau1ap, which they called Secp43. The 287-amino acid rat Secp43 protein is highly conserved and contains 2 RNA-binding domains and a polar/acidic C terminus. Northern blot analysis detected a 1.3-kb SECp43 transcript in HeLa cells and all rat tissues tested. Western blot analysis showed that human SECp43 had an apparent molecular mass of 43 kD in HeLa cells.
Using immunofluorescence analysis, Xu et al. (2005) showed that Secp43 localized primarily to nuclei of transfected NIH3T3 mouse embryonic fibroblasts.
Mahdi et al. (2015) stated that human SECp43 contains 2 RNA recognition motifs (RRM) and a C-terminal tyr-rich domain.
Gross (2021) mapped the TRNAU1AP gene to chromosome 1p35.3 based on an alignment of the TRNAU1AP sequence (GenBank BC000680) with the genomic sequence (GRCh38).
Mahdi et al. (2015) stated that the Trnau1ap gene maps to mouse chromosome 1.
Using affinity purification, Ding and Grabowski (1999) identified SECp43 as an RNA-binding protein that associated specifically with tRNA-sec in HeLa cells. Rat Secp53 also interacted specifically with a 48-kD protein in HeLa cell cytoplasmic extract.
Xu et al. (2005) found that Secp43 knockdown in NIH3T3 cells reduced the level of methylation at the 2-prime-hydroxylribosyl moiety in the wobble position (Um34) of tRNA-(ser)sec, leading to selective reduction of the amount of Gpx1 (138320). Immunoprecipitation analysis showed that Secp43 interacted with Sla (SEPSECS; 613009), another tRNA-(ser)sec-interacting protein, and that Secp43, Sla, and tRNA-(ser)sec formed a complex. Depletion of either of the 2 proteins affected binding of the other to tRNA-(ser)sec. Cotransfection of SECp43 and SLA in NIH3T3 cells suggested that SECp43 might also promote shuttling of tRNA-(ser)sec and cytoplasmic SLA between different cellular compartments.
Using a quantitative bioluminescence resonance energy transfer assay, Oudouhou et al. (2017) demonstrated that SECp43 interacted with other components of the selenocysteine machinery, including SEPHS1 (600902), SEPHS2 (606218), and SEPSECS, in HEK293T cells.
Hu et al. (2018) found that knockdown of the TRNAU1AP gene in NIH3T3 and human JEG-3 and Bewo choriocarcinoma cells reduced cellular antioxidant activity, inhibited cell migration and proliferation, and attenuated the PI3K (see 171834)/AKT (164730) signaling pathway.
Using X-ray scattering analysis of purified recombinant protein and structural modeling, Oudouhou et al. (2017) showed that human SECp43 had an a N-terminal globular region followed by a C-terminal unstructured region. SECp43 was present in monomeric and dimeric forms, and a consensus sequence between residues 163 and 169 (LGSKPVR), which localized on the surface of the second RRM domain, especially residues K166 and P167, were required for dimerization. In addition, the authors identified a region between residues 120 and 125 (GVHTVA) possibly corresponding to an interaction site for SECp43 and SEPSECS.
Mahdi et al. (2015) found that constitutive deletion of portion of the first RRM of Secp43 in mice produced no apparent phenotype and did not alter selenoprotein expression. However, constitutive deletion of the tyr-rich domain of Secp43 resulted in embryonic lethality. Although Secp43 is highly expressed in mouse liver, hepatocyte-specific deletion of the tyr-rich domain of Secp43 did not impair liver integrity, nor did it alter the selenoprotein expression. Quantitative PCR analysis confirmed that loss of Secp43 in liver was not compensated by alterations in hepatic selenoprotein and selenoprotein biosynthesis factor mRNA levels. In addition, methylation status and abundance of tRNA-(ser)sec remained unchanged in liver of mutant mice. Neuron-specific deletion of the tyr-rich domain of Secp43 also did not affect cerebral selenoprotein expression or cerebellar development, although these mutant mice did show impaired motor performance.
Ding, F., Grabowski, P. J. Identification of a protein component of a mammalian tRNA-Sec complex implicated in the decoding of UGA as selenocysteine. RNA 5: 1561-1569, 1999. [PubMed: 10606267] [Full Text: https://doi.org/10.1017/s1355838299991598]
Gross, M. B. Personal Communication. Baltimore, Md. 10/28/2021.
Hu, X., Luo, J., Lai, H., Li, M., Zheng, X., Nie, T., Li, F., Li, H. Knockdown of Trnau1ap inhibits the proliferation and migration of NIH3T3, JEG-3 and Bewo cells via the PI3K/Akt signaling pathway. Biochem. Biophys. Res. Commun. 503: 521-527, 2018. [PubMed: 29758194] [Full Text: https://doi.org/10.1016/j.bbrc.2018.05.065]
Mahdi, Y., Xu, X.-M., Carlson, B. A., Fradejas, N., Gunter, P., Braun, D., Southon, E., Tessarollo, L., Hatfield, D. L., Schweizer, U. Expression of selenoproteins is maintained in mice carrying mutations in SECp43, the tRNA selenocysteine 1 associated protein (Trnau1ap). PLoS One 10: e0127349, 2015. [PubMed: 26043259] [Full Text: https://doi.org/10.1371/journal.pone.0127349]
Oudouhou, F., Casu, B., Puemi, A. S. D., Sygusch, J., Baron, C. Analysis of novel interactions between components of the selenocysteine biosynthesis pathway, SEPHS1, SEPSH2, SEPSECS, and SECp43. Biochemistry 56: 2261-2270, 2017. [PubMed: 28414460] [Full Text: https://doi.org/10.1021/acs.biochem.6b01116]
Xu, X.-M., Mix, H., Carlson, B. A., Grabowski, P. J., Gladyshev, V. N., Berry, M. J., Hatfield, D. L. Evidence for direct roles of two additional factors, SECp43 and soluble liver antigen, in the selenoprotein synthesis machinery. J. Biol. Chem. 280: 41568-41575, 2005. [PubMed: 16230358] [Full Text: https://doi.org/10.1074/jbc.M506696200]