| 2021 |
Depletion of SNRPD2 (along with SNRPD3 and NHP2L1) inhibits proliferation of triple-negative breast cancer (TNBC) cells by deregulating sister chromatid cohesion (SCC) via increased sororin intron 1 retention and downregulation of SMC1, MAU2, and ESPL1. Protein-protein interaction analysis identified SNRPD2, SNRPD3, and NHP2L1 as belonging to the same spliceosome complex, which also includes novel component SUN2, critical for efficient sororin splicing. |
RNAi screen, western blot, PCR (intron retention), FACS, molecular imaging, pulldown + mass spectrometry for protein-protein interactions |
Journal of experimental & clinical cancer research |
Medium |
33648524
|
| 2022 |
Snrpb and Snrpd2 regulate exon-skipping patterns during zygotic genome activation (ZGA). These two core spliceosomal components have low maternal expression at ZGA and increase sharply thereafter. Microinjection of Snrpb/d2 mRNA into mouse zygotes reduces exon skipping at ZGA and leads to increased p53-mediated DNA damage response, establishing that developmentally programmed low expression of these factors contributes to splicing failure and attenuation of DNA damage response. |
Transcriptomic analysis of preimplantation embryos (human, mouse, cow), microinjection of mRNA into mouse zygotes, measurement of exon skipping and p53-mediated DDR |
Science advances |
Medium |
35417229
|
| 2022 |
SNRPD2 is a novel substrate for the E3 ubiquitin ligase activity of the Salmonella type III secretion effector SlrP. Yeast two-hybrid identified SNRPD2 as a human binding partner of SlrP, and in vitro ubiquitination assays confirmed SNRPD2 is ubiquitinated by SlrP but not by related NEL-family E3 ligases SspH1 or SspH2. The specific lysine residues modified were identified by mass spectrometry. |
Yeast two-hybrid (binding), in vitro ubiquitination assay, mass spectrometry (lysine site identification) |
Biology |
Medium |
36290420
|
| 2024 |
SNRPD2 (PD2) is the most highly upregulated Sm protein in hepatocellular carcinoma (HCC) and acts as an oncogene. Mechanistically, SNRPD2 cooperates with HNRNPL to modulate DDX39A intron retention, sustaining expression of a DDX39A short variant (39A_S). 39A_S mediates nuclear export of MYC mRNA to maintain high MYC protein expression, while MYC in turn potentiates SNRPD2 transcription, forming a positive feedback loop. The small molecule digitoxin can directly interact with SNRPD2 and suppresses HCC. |
Overexpression/knockdown functional assays, splicing analysis (intron retention), MYC mRNA nuclear export assays, drug binding (digitoxin-SNRPD2 interaction), in vivo tumor models |
Advanced science |
Medium |
39018261
|
| 2024 |
SNRPD2 interacts with the glutamic-proline (EP) domain of PABPN1 and disrupts PABPN1 liquid-liquid phase separation (LLPS). This disruption of PABPN1 LLPS attenuates PABPN1's repression of proximal poly(A) sites, leading to shortened 3' UTR of CTNNBIP1 and promoting colorectal cancer cell proliferation and migration. |
Co-immunoprecipitation (SNRPD2-PABPN1 interaction), LLPS assay, APA profiling, domain mapping, functional proliferation/migration assays |
Science China. Life sciences |
Medium |
38811444
|
| 2022 |
Free U1 snRNP proteins including SNRPD2 (when knocked down or overexpressed) promote usage of proximal alternative polyadenylation (APA) sites at the transcriptome level, contrary to the repressive effect of the intact U1 snRNP complex. This occurs through interaction with 3' end processing machinery. |
Knockdown and overexpression of SNRPD2 and other U1 snRNP proteins, transcriptome-wide APA profiling, phase transition assays, co-immunoprecipitation |
Journal of molecular cell biology |
Medium |
36073763
|
| 2022 |
Silencing of SNRPD2 in HCC cell lines results in impaired proliferation and G1/M cell cycle arrest, accompanied by downregulation of transcription-cycle-related genes. |
siRNA knockdown of SNRPD2, cell proliferation assay, cell cycle analysis (FACS), gene expression analysis |
Diagnostics |
Low |
35626291
|
| 2024 |
SNRPD2 silencing using shRNA-expressing lentiviral vectors selectively inhibits viability of cancer cell lines (including short-term cultured melanoma cells) but not normal cell cultures, establishing SNRPD2 as a cancer-selective lethal target. Genes with similar essentiality profiles implicate SNRPD2 in mRNA splicing, coordinated protein production, and mitosis. |
shRNA lentiviral knockdown, cell viability assays across cancer and normal cell lines, analysis of public cell viability datasets (DepMap), essentiality profile correlation |
International journal of molecular sciences |
Medium |
39684842
|
| 2026 |
Mutant p53 (mtp53) physically binds SNRPD2 and cooperates with it to facilitate assembly of the Sm/SMN protein complex, an essential spliceosome component, thereby modulating alternative splicing of pre-mRNAs. Co-depletion of mtp53 and SNRPD2 reduces oncogenic OTUD3 transcripts and increases tumor-suppressor OTUD3 counterparts through an exon-skipping event. |
Co-immunoprecipitation (mtp53-SNRPD2 interaction), overexpression/depletion functional assays, alternative splicing analysis (exon skipping of OTUD3), in vivo xenograft models with engineered exosomes delivering siRNAs |
Advanced science |
Medium |
41560375
|
| 2026 |
SNRPD2 knockdown induces retention of intron 5 in DDX39B pre-mRNA, producing a noncoding transcript degraded by nonsense-mediated decay (NMD), thereby reducing DDX39B expression. Reduced DDX39B levels permit activation of a cryptic exon (Exon 2_3) in CTSC mRNA, introducing premature termination codons and triggering additional NMD-mediated CTSC degradation. Antisense oligonucleotides (ASOs) targeting SNRPD2 reduce tumor growth in a patient-derived xenograft model, establishing the SNRPD2-DDX39B-CTSC regulatory axis. |
SNRPD2 knockdown, intron retention/splicing analysis, NMD pathway assays, cryptic exon analysis, ASO treatment, patient-derived xenograft (PDX) in vivo model |
Cell death & disease |
Medium |
41720762
|
| 2026 |
SNRPD2 knockdown induces exon 4 skipping in CPSF7 pre-mRNA, disrupting the RNA recognition motif (RRM) domain essential for CPSF7-mediated pre-mRNA cleavage and polyadenylation, and introducing premature termination codons that trigger NMD-mediated CPSF7 degradation. CPSF7 in turn governs APA events controlling UBE2K transcript stability. This defines a SNRPD2-CPSF7-UBE2K axis linking alternative splicing to alternative polyadenylation in ovarian cancer. |
SNRPD2/CPSF7 knockdown, exon skipping analysis, NMD assays, APA profiling, functional proliferation/migration assays, PDX model with ASOs |
Oncogene |
Medium |
42098443
|
| 2026 |
NKRF directly represses transcription of SNRPD2, thereby constraining stress granule formation and attenuating drug tolerance to Osimertinib. The E3 ubiquitin ligase TRIM26 interacts with NKRF and promotes its K48-linked ubiquitination at Lys411, leading to proteasomal degradation, which in turn sustains SNRPD2 expression and enhances stress granule assembly. Genetic depletion of TRIM26 restored NKRF stability, suppressed stress granule formation, and re-sensitized resistant tumors to Osimertinib. |
Co-immunoprecipitation (TRIM26-NKRF interaction), ubiquitination assays (K48-linkage, Lys411 site), transcriptional reporter assays, SNRPD2 knockdown/overexpression, stress granule imaging, in vivo xenograft models |
Cell death & disease |
Medium |
42026030
|
| 1999 |
Sm-D2 (SNRPD2) is recognized by anti-Sm autoantibodies in systemic lupus erythematosus, but with distinct antibody recognition patterns from Sm-D1 and Sm-D3. Human and murine lupus sera showed two patterns: Sm-D1/D3 (predominant) or Sm-D1/D2/D3. None of the MRL-derived monoclonal anti-Sm antibodies reacted with Sm-D2. Immunization with isolated Sm-D (containing all three D antigens) from rabbit thymus produced autoantibody reactive only with Sm-D2, indicating distinct antigenic epitopes among the Sm-D family members. |
Protein immunoblot screening of human and murine sera, monoclonal antibody panel screening, immunization with isolated Sm-D antigen |
Clinical immunology |
Medium |
10444365
|