| 1992 |
SLU7 is required for second catalytic step of pre-mRNA splicing and mediates 3' splice site choice; mutations in SLU7 eliminate the normal 20-fold preference for 3' splice sites located >22 nucleotides downstream of the branchpoint. SLU7 contains a zinc knuckle motif (similar to retroviral nucleocapsid proteins) that influences the efficiency, but not sequence specificity, of 3' splice site selection. SLU7 is an essential gene in yeast. |
Genetic analysis of SLU7 mutants; competing 3' splice site assays; mutational analysis of zinc knuckle motif |
Genes & development |
High |
1427075
|
| 1995 |
SLU7 protein acts during the PRP16-dependent step of splicing and can function after PRP16 in the splicing pathway. SLU7 and a novel factor SSF1 are required in concert with PRP16 to promote progression through the second catalytic step of splicing. |
Glycerol gradient sedimentation of spliceosomes; in vitro reconstitution with purified proteins; differential ATP requirement assay |
The EMBO journal |
High |
7664739
|
| 1996 |
SLU7 is only required for splicing when the interval between the branchpoint and the 3' splice site is greater than 7 nucleotides; it is dispensable for splicing of RNAs with short branchpoint-to-3'SS distances. SLU7 is a spliceosome component (shown by immunoprecipitation), its recruitment is greatly enhanced by prior addition of PRP16, and SLU7 remains bound to the excised intron and spliced mRNA after step 2 until spliceosome disassembly (ATP-dependent). |
In vitro splicing assays with natural and model pre-mRNAs; anti-SLU7 immunoprecipitation of spliceosomal complexes |
RNA (New York, N.Y.) |
High |
8756413
|
| 1997 |
SLU7 physically interacts with Prp18; the Prp18 interaction domain maps to residues 200–224 of Slu7. Excess Slu7 can bypass the need for Prp18 in vitro, indicating they function in a concerted manner. Prp18 requirement is also dictated by branchpoint-to-3'SS distance (<12 nt makes Prp18 dispensable), paralleling SLU7 requirements. |
Two-hybrid assay; in vitro splicing bypass experiments; deletion mutagenesis of SLU7 |
Nucleic acids research |
High |
9153314
|
| 2002 |
Slu7 contains two functionally important domains: a zinc knuckle (residues 122–135) and a Prp18-interaction domain (residues 215–224). Zinc knuckle mutations (C122A, H130A, C135A) make Slu7 spliceosome binding dependent on Prp18. Alanine mutations in the Prp18-interaction domain abrogate binding to Prp18 in two-hybrid and in vitro assays but do not impair splicing alone; compound mutations in both domains are lethal and abolish splicing. Second-step factors are recruited in the order Slu7 → Prp18 → Prp22, and all three are released after step 2 concomitant with mRNA release. |
Alanine cluster mutagenesis; two-hybrid assay; in vitro splicing reconstitution; depletion/reconstitution immunoprecipitations |
RNA (New York, N.Y.) |
High |
12212850
|
| 2013 |
Fission yeast SpSlu7 has widespread intron-specific splicing functions; a missense mutant reveals global splicing derangements. Features including branchpoint-to-3'SS distance, intron length, and A/U content at the intron 5' end determine SpSlu7 dependence. Unexpectedly, an early splicing arrest in the spslu7-2 mutant reveals a role before catalysis. SpSlu7 shows a salt-stable association with U5 snRNP and genetic interactions with spprp1+ (homolog of human U5-102k), suggesting a role in facilitating spliceosome transitions that promote catalysis. |
Missense mutant analysis; global splicing assays; co-fractionation/salt-stability assay with U5 snRNP; genetic interaction analysis |
Molecular and cellular biology |
Medium |
23754748
|
| 2014 |
Human SLU7 knockdown in liver cells and mouse liver causes profound changes in pre-mRNA splicing and gene expression, impairs glucose and lipid metabolism, increases proliferation, and reverts hepatocytes to a fetal-like gene expression pattern. SLU7 governs splicing and/or expression of SRSF3 and HNF4α, key hepatocellular differentiation genes, and is critical for cAMP-regulated gene transcription. |
siRNA knockdown in human liver cells and mouse liver; RNA-seq; gene expression analysis |
The Journal of clinical investigation |
Medium |
24865429
|
| 2016 |
SLU7 binds the C13orf25 primary transcript that encodes the miR-17-92 cluster and is required for its processing and expression. SLU7 knockdown alters splicing of C13orf25, reducing miR-17, miR-20, and miR-92a levels, leading to upregulation of CDKN1A (p21) and BCL2L11 (BIM). Rescue with miR-17 mimic reversed oxidative stress, autophagy and apoptosis upon SLU7 KD in HCC cells. |
RNA binding/co-immunoprecipitation of SLU7 with C13orf25 transcript; splicing analysis; miRNA expression; miR-17 mimic rescue experiments |
Oncogene |
Medium |
26804174
|
| 2019 |
SLU7 knockdown results in R-loop formation, DNA damage, cell-cycle arrest, and severe mitotic derangements including loss of sister chromatid cohesion (SCC). SLU7 controls generation of truncated SRSF3 (SRSF3-TR); SRSF3-TR acts as a dominant negative/gain-of-function to impair splicing of SRSF1 and the SCC protein sororin, linking SLU7 to genome integrity through a SLU7→SRSF3 splicing→SRSF1/sororin pathway. |
siRNA knockdown; R-loop detection; DNA damage assays; mitotic analysis; splicing analysis; epistasis/pathway placement |
Nucleic acids research |
Medium |
30657957
|
| 2021 |
SLU7 is required to maintain DNMT1 protein stability and correct DNA methylation. SLU7 is part of the chromatome complex with DNMT1, its adaptor UHRF1, and histone methyltransferase G9a. Mechanistically, SLU7 prevents DNMT1 acetylation and degradation by facilitating DNMT1 interaction with HDAC1 and the deubiquitinase USP7. |
Mass spectrometry (chromatome); co-immunoprecipitation; SLU7 knockdown/KO in multiple cell lines and in vivo liver proliferation models; DNA methylation assays |
Nucleic acids research |
Medium |
34331453
|
| 2021 |
SLU7 protects HNF4α1 protein stability against oxidative stress-induced degradation, thereby preserving hepatic differentiation. SLU7 is identified as a key component of the stress granule proteome (by mass spectrometry of the SLU7 interactome), placing it in the cell's antioxidant machinery. SLU7 haploinsufficiency in mice increases sensitivity to chronic (CCl4) and acute (acetaminophen) liver injury, with enhanced oxidative stress and impaired hepatic function; AAV-SLU7 delivery prevents injury and dedifferentiation. |
Mass spectrometry of SLU7 interactome; Slu7+/- mouse model; AAV-SLU7 rescue; western blotting for HNF4α protein stability |
Hepatology (Baltimore, Md.) |
Medium |
34170569
|
| 2023 |
SLU7 interacts with G3BP1 to form a complex with PABPC1 and eIF4G1 that stabilizes the closed-loop structure of class IA PI3K mRNAs, facilitating their translation and stabilization, thereby activating PI3K/Akt signaling to downregulate MHC-I expression in bladder cancer cells. |
Co-immunoprecipitation; pulldown assays; SLU7 knockdown in bladder cancer cells; PI3K/Akt pathway activity assays; MHC-I expression analysis |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
Medium |
38084438
|
| 2024 |
SLU7 interacts with the NMD effector UPF1 and preserves UPF1 protein levels, and SLU7 is required for correct nonsense-mediated mRNA decay (NMD). Caspases activated during liver damage cleave and degrade SLU7, mechanistically linking apoptotic signaling to SLU7 downregulation and NMD inhibition. |
Co-immunoprecipitation of SLU7 with UPF1; SLU7 knockdown NMD assays; animal models of liver injury; western blotting for caspase-mediated cleavage |
JHEP reports : innovation in hepatology |
Medium |
39105183
|
| 2025 |
THRAP3 recruits SLU7 to facilitate GIT2 Exon14 skipping, promoting ferroptosis resistance in AML cells. Inhibition of GIT2 Exon14 skipping reverses THRAP3-induced ferroptosis resistance. |
Co-immunoprecipitation of THRAP3 with SLU7; SLU7 knockdown/overexpression; GIT2 splicing analysis; ferroptosis assays in vitro and in vivo |
Nature communications |
Medium |
41326370
|
| 2026 |
NAA50 catalyzes N-terminal acetylation of SLU7, preventing its ubiquitin-proteasomal degradation and sustaining SLU7 stability. SLU7 directly binds MAP3K3 mRNA and promotes its nuclear export (a non-canonical, splicing-independent function), activating p38 MAPK signaling and driving cisplatin resistance in bladder cancer. |
Mass spectrometry; co-immunoprecipitation; RIP-qPCR (SLU7-MAP3K3 mRNA binding); RNA-FISH and nucleocytoplasmic fractionation; NAA50 pharmacological inhibition; xenograft models |
Cellular oncology (Dordrecht, Netherlands) |
Medium |
42151695
|
| 2018 |
In the context of alcoholic liver disease, SLU7 knockdown increased SIRT1 full-length expression while repressing splicing of SIRT1 into the SIRT1-ΔExon8 isoform. SLU7 knockdown also ameliorated splicing of lipin-1 and SRSF3, inhibited NF-κB activity, and reduced oxidative stress. |
Adenovirus-mediated SLU7 shRNA knockdown in mice; isoform-specific RT-PCR; NF-κB activity assays; oxidative stress markers |
The American journal of pathology |
Medium |
29870742
|