| 2000 |
SBP2 was purified and identified as a novel SECIS RNA-binding protein essential for co-translational selenocysteine incorporation. Immunodepletion of SBP2 from cell lysates abolished selenocysteine insertion, which was restored by adding recombinant SBP2, establishing its essential role in Sec incorporation in vitro. |
UV cross-linking, immunoprecipitation, in vitro translation with 75Se-labeled Sec-tRNA, immunodepletion and add-back reconstitution |
The EMBO journal |
High |
10637234
|
| 2000 |
SBP2 overexpression overcomes competition for selenoprotein synthesis caused by excess selenoprotein mRNA, and SBP2 once bound to SECIS elements does not readily exchange between them. SBP2 preferentially stimulates selenocysteine incorporation directed by selenoprotein P and PHGPx SECIS elements over those of other selenoproteins, establishing its role in determining a hierarchy of selenoprotein synthesis. |
Transfection-based competition assay, co-expression of SBP2 and selenoprotein mRNAs in cells |
The EMBO journal |
High |
11118223
|
| 2001 |
SBP2 binds the proximal part of SECIS hairpin, protecting 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 prevents SBP2 binding. |
Enzymatic and hydroxyl radical footprinting, gel mobility shift assay, phosphate-ethylation binding interference |
RNA (New York, N.Y.) |
High |
11680849
|
| 2002 |
SBP2 and the U4 snRNA-binding protein 15.5 kD/Snu13p share the same L7A/L30 family RNA binding domain. Structure-guided alanine substitution of 12 predicted residues identified four whose mutation severely diminished or abolished SECIS RNA binding, mapping critical amino acids for SECIS recognition by SBP2. |
Multiple sequence alignment, structure-guided mutagenesis, alanine substitution, gel shift assays |
RNA (New York, N.Y.) |
High |
12403468
|
| 2007 |
SBP2 exhibits strong preferential binding to some selenoprotein mRNAs over others in vivo, and knockdown of SBP2 expression leads to differential effects on selenoprotein mRNA levels and sensitivity to nonsense-mediated decay, establishing SBP2 as a major determinant of the hierarchy of selenoprotein synthesis. |
siRNA knockdown of SBP2, immunoprecipitation of SBP2 followed by quantitative RT-PCR of bound mRNAs |
Molecular and cellular biology |
High |
17846120
|
| 2008 |
Alternative splicing of human SECISBP2 produces at least eight splice variants encoding 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 are subject to 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 fluorescence microscopy, UVA stress experiments |
Nucleic acids research |
Medium |
19004874
|
| 2014 |
SBP2 contacts the human ribosome primarily through the 28S rRNA at helix ES7L-E in expansion segment 7 of the 60S subunit. SBP2 binding to ribosomes induces conformational changes in ES7L-E and the universally conserved helix H89 of 28S rRNA. |
Bifunctional reagent cross-linking, hydroxyl radical probing of 28S rRNA, diepoxybutane cross-linking, chemical probing |
RNA (New York, N.Y.) |
High |
24850884
|
| 2017 |
Ribosome profiling and RNA-Seq in mouse liver with conditional deletion of Secisbp2 or Trsp (tRNASec) revealed that Secisbp2 has two separable functions: facilitating Sec incorporation at UGA codons and stabilizing selenoprotein mRNAs. Loss of tRNASec uniformly abolished ribosome density downstream of UGA-Sec codons, while loss of Secisbp2 produced gene-specific variable effects. For several selenoproteins, Secisbp2 loss reduced mRNA levels without affecting translational activity on remaining mRNA, demonstrating a distinct mRNA stability role. |
Ribosome profiling, RNA-Seq, mRNA half-life measurements, conditional knockout mouse models (Secisbp2 and Trsp), genetic epistasis comparison |
Nucleic acids research |
High |
27956496
|
| 2019 |
Two pathogenic missense mutations in Secisbp2 were functionally dissected in mouse models: C696R in the RNA-binding domain abrogates SECIS binding and does not support selenoprotein translation above the null level; R543Q in the selenocysteine insertion domain causes residual activity but is thermally unstable in vitro and completely degraded in mouse liver while being partially functional in the brain, demonstrating that differential protein stability in individual cell types dictates tissue-specific phenotypes. |
Mouse knockin models with pathogenic mutations, ribosome profiling, in vitro thermal stability assay, Western blotting |
The Journal of biological chemistry |
High |
31350336
|
| 2005 |
Homozygous or compound heterozygous missense mutations in SECISBP2 in humans cause decreased DIO2 enzymatic activity and generalized selenoprotein deficiency, establishing SBP2 as epistatic to selenoprotein synthesis in vivo. The phenotype includes abnormal thyroid hormone metabolism with reduced T3, elevated T4, and reduced glutathione peroxidase and selenoprotein P levels. |
Genetic linkage analysis, fibroblast DIO2 enzyme activity assay, sequencing of SECISBP2 gene, in vivo human studies |
Nature genetics |
High |
16228000
|
| 2010 |
The R770X truncation mutation in SBP2 specifically inhibits its binding to SECIS elements in vitro, as demonstrated by gel shift assay, while R120X disrupts all functional motifs. This establishes the C-terminal region (around residue 770) as required for SECIS RNA binding. |
Gel shift assay with mutant SBP2 proteins, DNA sequencing |
The Journal of clinical endocrinology and metabolism |
Medium |
20501692
|
| 2009 |
The R128X nonsense mutation in SBP2 allows synthesis of SBP2 isoforms from at least three downstream ATGs that contain all essential functional domains, explaining the relatively mild phenotype caused by an early stop codon. This demonstrates that internal translation initiation can produce functional SBP2 isoforms. |
Minigene construction, in vitro translation analysis, clinical phenotyping |
The Journal of clinical endocrinology and metabolism |
Medium |
19602558
|
| 2019 |
SBP2 deficiency in adipose tissue macrophages (ATMs) promotes metabolic activation, increases intracellular reactive oxygen species and inflammasome activity, and promotes IL-1β-associated local proliferation and infiltration of proinflammatory macrophages. ATM-specific SBP2 knockdown in obese mice promoted insulin resistance, while reexpression of SBP2 improved insulin sensitivity. |
ATM-specific knockdown in vivo in obese mice, ROS measurement, inflammasome assays, metabolic phenotyping |
Science advances |
Medium |
31453320
|
| 2025 |
CRISPR-Cas9 knockout of SBP2 in HepG2 cells impairs selenoprotein mRNA and protein expression with a transcriptomic signature enriched for metabolic and ion transport processes, distinct from that of the paralog SECISBP2L. SBP2 targeting confirmed its canonical role in selenoprotein synthesis while demonstrating it does not regulate extracellular matrix or cell adhesion pathways (those are SECISBP2L-specific). |
CRISPR-Cas9 knockout, RNA-seq, mass spectrometry, immunoblotting |
bioRxivpreprint |
Medium |
bio_10.1101_2025.07.02.662884
|