| 1999 |
SECp43 (TRNAU1AP) was identified as a novel RNA-binding protein that associates specifically with mammalian selenocysteine tRNA (tRNA(Sec)), demonstrated by affinity purification of tRNA(Sec) from HeLa cell extracts using an anti-SECp43 antibody column. Recombinant SECp43 also pulled down a 48-kDa interacting protein, suggesting it participates in a multi-component selenocysteine insertion complex. |
Antibody affinity purification, recombinant protein pulldown, Northern blot, direct RNA sequencing |
RNA |
Medium |
10606267
|
| 2005 |
Knockdown of SECp43 in NIH3T3 and TCMK-1 cells by RNAi reduced methylation at the 2'-hydroxylribosyl moiety at the wobble position (Um34) of Sec tRNA([Ser]Sec), consequently reducing glutathione peroxidase 1 expression. SECp43 forms a complex with Sec tRNA([Ser]Sec) and SLA (soluble liver antigen), and loss of one protein affects the other's binding to the tRNA. SECp43 is located primarily in the nucleus; co-transfection with SLA caused nuclear translocation of SLA, suggesting SECp43 promotes shuttling of SLA and Sec tRNA between compartments. |
RNAi knockdown, methylation analysis of tRNA, co-immunoprecipitation, subcellular fractionation/localization, Western blot |
The Journal of biological chemistry |
High |
16230358
|
| 2006 |
SECp43 interacts with the selenocysteyl-tRNA([Ser]Sec)-EFsec complex in vitro. SECp43 co-expression promotes interaction between EFsec and SBP2 in vivo. SECp43 cotransfection with SLA/LP and SPS1 increases SLA/LP–SPS1 interaction and redistributes all three proteins to a predominantly nuclear localization. SECp43 overexpression increases selenocysteine incorporation and selenoprotein mRNA levels (the latter presumably via circumvention of nonsense-mediated decay). |
In vitro binding assay, co-immunoprecipitation, subcellular localization (transfection + imaging), selenocysteine incorporation assay, mRNA level measurement |
Molecular and cellular biology |
High |
16508009
|
| 2017 |
SECp43 forms oligomers in eukaryotic cells, as demonstrated by BRET assay. Small-angle X-ray scattering of recombinant SECp43 revealed it is a globular protein comprising two RNA-binding domains. Phage display identified two residues (K166 and P167) required for SECp43 dimerization. SECp43 also interacts with selenocysteine synthase (SEPSECS) in mammalian cells (confirmed by BRET and co-immunoprecipitation). |
Bioluminescence resonance energy transfer (BRET), co-immunoprecipitation, small-angle X-ray scattering (SAXS), phage display mutagenesis |
Biochemistry |
High |
28414460
|
| 2015 |
Constitutive deletion of SECp43 exons 7+8 in mice was embryonic lethal. Hepatocyte-specific deletion of exons 7+8 showed no significant changes in selenoprotein levels, tRNA([Ser]Sec) Um34 methylation, or selenoprotein mRNA abundance in liver, indicating the deleted domains are not essential for selenoprotein biosynthesis in hepatocytes. However, neuron-specific deletion of exons 7+8 impaired motor performance without affecting cerebral selenoprotein expression or cerebellar development, revealing a non-selenoprotein function in neurons. Truncated Secp43 mRNA increased in mutant livers, suggesting auto-regulation of Secp43 mRNA abundance. |
Conditional knockout mouse models, 75Se labeling, Western blot, enzymatic activity assays, tRNA methylation analysis, behavioral motor tests |
PloS one |
High |
26043259
|
| 2016 |
Knockdown of Trnau1ap in H9c2 cardiomyocyte-like cells reduced expression of glutathione peroxidase, thioredoxin reductase, and selenoprotein K; inhibited cell proliferation; and induced apoptosis with increased Bax and decreased Bcl-2 expression. Overexpression promoted cell growth. PI3K/Akt signaling pathway was activated in Trnau1ap-underexpressing cells. |
siRNA knockdown, overexpression plasmid transfection, MTT/PCNA/Annexin V/caspase-3 assays, Western blot |
Molecular medicine reports |
Medium |
28101579
|
| 2018 |
Lentiviral shRNA knockdown of Trnau1ap in NIH3T3, JEG-3, and Bewo cells reduced selenoprotein expression, decreased cell proliferation and migration, and attenuated Akt phosphorylation in the PI3K/Akt pathway. |
Lentiviral shRNA knockdown, CCK-8 proliferation assay, wound scratch migration assay, Western blot for p-Akt |
Biochemical and biophysical research communications |
Medium |
29758194
|
| 2024 |
Tethered function splicing reporter assays and enhanced cross-linking immunoprecipitation (eCLIP) combined with RNA sequencing and affinity purification-mass spectrometry revealed that TRNAU1AP modulates hundreds of endogenous splicing events, indicating a direct role in alternative splicing in addition to its known function in selenocysteine incorporation. |
Tethered function luciferase splicing reporters (718 RBPs screened), eCLIP, RNA sequencing, affinity purification-mass spectrometry |
Nature biotechnology |
Medium |
38168984
|
| 2026 |
TRNAU1AP interacts with EEFSEC (the selenocysteine-specific elongation factor) and forms a phase-separated complex that enhances EEFSEC binding to sec-tRNA(sec), thereby promoting translation of multiple selenoproteins in glioblastoma stem cells. IGF2BP3 upregulates TRNAU1AP expression through m6A-dependent transcript stabilization. Loss of TRNAU1AP impairs glioblastoma stem cell proliferation, self-renewal, and tumorigenesis. |
RNA immunoprecipitation, phase-separation assays, polysome profiling, proteomics, spatial transcriptomics, gain- and loss-of-function assays, RNA stability analysis |
Neuro-oncology |
High |
42080969
|