| 2000 |
SBP2 was purified as a SECIS-binding protein and shown to be essential for co-translational selenocysteine insertion. Immunodepletion of SBP2 from cell lysates abolished selenocysteine incorporation into selenoprotein mRNAs in vitro, and this was rescued by adding back recombinant SBP2. The activity was both SBP2- and SECIS element-dependent. |
UV cross-linking, immunoprecipitation, in vitro Sec incorporation assay with 75Se-labeled Sec-tRNA, immunodepletion and recombinant protein rescue |
The EMBO journal |
High |
10637234
|
| 2000 |
SBP2 recruits the selenocysteine-specific elongation factor (eEFSec) to selenoprotein mRNA via SECIS binding. Overexpression of SBP2 (but not selenocysteyl-tRNA or eEFSec) overcame competition from excess selenoprotein mRNAs, establishing SBP2 as the limiting trans-acting factor. SBP2, once bound to SECIS elements, does not readily exchange between them. SBP2 preferentially stimulates selenocysteine incorporation from selenoprotein P and PHGPx SECIS elements over others, establishing a hierarchy of selenoprotein synthesis. |
Transfection-based competition assay, co-expression of trans-acting factors, overexpression of selenoprotein mRNAs |
The EMBO journal |
High |
11118223
|
| 2001 |
SBP2 binds to a conserved site on SECIS RNA hairpins: it protects the proximal part of the hairpin and both strands of the lower half of the upper helix containing the non-Watson-Crick G·A/A·G base-pair quartet. The G·A/A·G tandem and internal loop are critical for SBP2 binding. Phosphate modification along both strands of the non-Watson-Crick base-pair quartet, the 5' strand of the lower helix, and part of the 5' strand of the internal loop prevented SBP2 binding. |
Enzymatic and hydroxyl radical footprinting, gel mobility shift analysis, phosphate-ethylation binding interference |
RNA (New York, N.Y.) |
High |
11680849
|
| 2002 |
SBP2 shares an RNA-binding domain of the L7A/L30 family with the U4 snRNA-binding protein 15.5 kD/Snu13p. Structure-guided alanine scanning of 12 SBP2 residues predicted from alignment with the 15.5 kD–U4 snRNA crystal structure identified four residues whose mutation severely diminished or abolished SECIS RNA binding, with the other eight causing intermediate effects, defining the key amino acids for SECIS recognition. |
Multiple sequence alignment, structure-guided alanine mutagenesis, gel shift assays |
RNA (New York, N.Y.) |
High |
12403468
|
| 2005 |
Homozygous and compound heterozygous missense mutations in SECISBP2 in humans cause a global defect in selenoprotein synthesis, resulting in abnormal thyroid hormone metabolism. SBP2 is epistatic to selenoprotein synthesis, so its partial loss has a generalized effect on selenoproteins including deiodinase 2. |
Genetic linkage analysis, sequencing, fibroblast DIO2 enzymatic activity assay |
Nature genetics |
High |
16228000
|
| 2007 |
SBP2 exhibits strong preferential binding to some selenoprotein mRNAs over others in vivo (determined by immunoprecipitation and mRNA quantitation), whereas nucleolin exhibits minimal differences in binding. Knockdown of SBP2 confirmed that SBP2 binding affinity is a major determinant dictating the hierarchy of selenoprotein synthesis via differential mRNA translation and sensitivity to nonsense-mediated decay. |
SBP2 knockdown by siRNA, immunoprecipitation of SBP2 followed by mRNA quantitation, selenoprotein mRNA level measurement |
Molecular and cellular biology |
High |
17846120
|
| 2008 |
Alternative splicing of SECISBP2 produces at least five isoforms with varying N-terminal sequences. One isoform, mtSBP2, contains a mitochondrial targeting sequence and localizes to mitochondria. Full-length SBP2 and some splice variants undergo coordinated transcriptional and translational regulation in response to UVA irradiation-induced stress. |
In silico analysis, minigene-based in vivo splicing assay, antisense oligonucleotide modulation, subcellular localization by mitochondrial targeting sequence identification and localization |
Nucleic acids research |
Medium |
19004874
|
| 2009 |
A nonsense mutation R128X in SBP2 results in synthesis of shorter SBP2 isoforms from at least three downstream ATGs, all of which retain the essential functional domains for SECIS binding. This explains why a severe truncating mutation produces a relatively mild phenotype of partial SBP2 deficiency. |
Sequencing, minigene construction, in vitro translation analysis of mutant proteins |
The Journal of clinical endocrinology and metabolism |
Medium |
19602558
|
| 2010 |
The SBP2 truncation mutation R770X (in the RNA-binding domain) inhibits binding of SBP2 to SECIS elements, as shown by gel shift assay, whereas R120X disrupts all functional motifs. Compound heterozygous R120X/R770X causes widespread selenoprotein deficiency including undetectable selenoprotein P. |
Gel shift assay of mutant SBP2 proteins, sequencing, selenoprotein P measurement |
The Journal of clinical endocrinology and metabolism |
Medium |
20501692
|
| 2014 |
SBP2 contacts the human ribosome primarily through the 28S rRNA at expansion segment ES7L, specifically helix ES7L-E. SBP2 binding to 80S ribosomes or 60S subunits protects helix ES7L-E from hydroxyl radical cleavage and induces conformational changes in ES7L-E and the universally conserved helix H89 of the 28S rRNA. |
Cross-linking with bifunctional reagents (diepoxybutane), direct hydroxyl radical probing of 28S rRNA, chemical probing |
RNA (New York, N.Y.) |
High |
24850884
|
| 2017 |
Ribosome profiling and RNA-seq of conditional Secisbp2 and Trsp (tRNA-Sec) knockout mouse livers showed that Secisbp2 loss results in gene-specific (variable) effects on ribosome density downstream of UGA-Sec codons, distinct from the uniform loss seen with tRNA-Sec depletion. For several selenoproteins, Secisbp2 loss greatly reduced mRNA levels without affecting translational activity or Sec incorporation efficiency on remaining RNA. These data demonstrate that Secisbp2 has a distinct role in stabilizing selenoprotein mRNAs separable from its role in UGA redefinition, and that Secisbp2 is not strictly required for Sec incorporation. |
Ribosome profiling, RNA-seq, mRNA half-life measurements, conditional genetic knockout (Cre-lox) in mouse liver |
Nucleic acids research |
High |
27956496
|
| 2017 |
Sbp2 conditional knockout mice have decreased deiodinase 1 expression and enzymatic activity in liver, decreased deiodinase 2 enzymatic activity and deiodinase 3 expression in cerebrum, and decreased expression of other selenoproteins in brain, liver, and serum, demonstrating that SBP2 deficiency causes global selenoprotein synthesis impairment with organ-specific effects on thyroid hormone metabolism. |
Tamoxifen-inducible conditional knockout mouse model, deiodinase enzymatic activity assays, selenoprotein expression analysis, serum thyroid hormone measurements |
Endocrinology |
High |
29029094
|
| 2019 |
Pathogenic missense mutation C696R in the RNA-binding domain of SECISBP2 abrogates SECIS binding and does not support selenoprotein translation above the level of a complete null mutation. The R543Q missense mutation in the selenocysteine insertion domain results in residual translational activity but causes thermally unstable protein that is completely degraded in mouse liver in vivo while being partially functional in brain, demonstrating that cell-type-specific protein stability dictates clinical phenotypes. |
Mouse knock-in models of patient mutations, ribosome profiling, in vitro thermal stability assay, immunoblot for protein levels in different tissues |
The Journal of biological chemistry |
High |
31350336
|
| 2019 |
SBP2 deficiency in adipose tissue macrophages (ATMs) causes increased intracellular reactive oxygen species and inflammasome activation, leading to IL-1β-driven proinflammatory macrophage expansion. ATM-specific knockdown of SBP2 in obese mice promoted insulin resistance via increased fat tissue inflammation; re-expression of SBP2 improved insulin sensitivity. |
ATM-specific siRNA knockdown in obese mice, re-expression experiments, ROS and inflammasome measurements, insulin sensitivity assays |
Science advances |
Medium |
31453320
|
| 2025 |
SBP2 targeting in HepG2 cells (CRISPR-Cas9) impaired selenoprotein mRNA and protein expression, confirming its essential role in selenoprotein synthesis in human hepatocytes, while producing a transcriptomic signature enriched for metabolic and ion transport processes distinct from that of its paralog SECISBP2L. |
CRISPR-Cas9 gene editing, RNA-seq, mass spectrometry, immunoblot |
bioRxivpreprint |
Medium |
bio_10.1101_2025.07.02.662884
|