| 1998 |
Crystal structure at 2.4 Å of the ternary U2B"/U2A'/U2 snRNA hairpin-loop IV complex revealed that the concave surface of the leucine-rich-repeat (LRR) parallel beta-sheet of U2A' interacts with the RRM domain of U2B" on the surface opposite its RNA-binding surface, while the basic C-terminal region of U2A' contacts the RNA stem. This protein-protein interaction is required for RNA-binding specificity of U2B", explaining how U2B" discriminates U2 hairpin IV from U1 hairpin II. |
X-ray crystallography (2.4 Å resolution) of recombinant ternary complex |
Nature |
High |
9716128
|
| 1991 |
U2A' forms a weak but detectable direct interaction with U2 RNA and a stable protein-protein complex with U2B"; the combined U2A'-U2B" complex binds U2 RNA efficiently and specifically. Mutational analysis mapped the U2B"-binding region of U2A' to amino acids 1-164, and mutation of residues 3-5 of U2A' reduced RNA binding, indicating U2A' contacts the stem of hairpin IV to stabilize the trimeric complex. |
RNA-protein and protein-protein binding assays with deletion/point mutants of U2A' and U2 RNA |
Nucleic acids research |
High |
1826350
|
| 1998 |
U2A' enables U2B" to discriminate the loop sequence of U2hpIV from U1hpII but plays no role in stem sequence discrimination. U2A' binds U2B" with ~500-fold higher affinity than U1A, and a single leucine residue (Leu-44) in U1A is critical for its intrinsic specificity for U1hpII over U2hpIV. |
In vitro RNA-binding and protein-protein interaction assays with point mutants; quantitative affinity measurements |
RNA (New York, N.Y.) |
High |
9814759
|
| 1998 |
Yeast ortholog Lea1p (U2A') is a specific component of the yeast U2 snRNP. Lea1p directly interacts with Yib9p (U2B" ortholog); in vivo association of Lea1p with U2 snRNA requires Yib9p, and reciprocally Yib9p requires Lea1p for U2 snRNA association in vivo. Strains lacking LEA1 and/or YIB9 have impaired pre-mRNA splicing, and in vitro spliceosome assembly is blocked prior to U2 snRNP addition; this defect is rescued by addition of recombinant protein(s). |
Genetic deletion (lea1Δ, yib9Δ), in vitro spliceosome assembly rescue with recombinant proteins, co-immunoprecipitation/co-purification with U2 snRNA |
The EMBO journal |
High |
9799242
|
| 2001 |
Drosophila U2A' protein interacts with SNF (U2B" ortholog) in vivo and is U2 snRNP-specific. Loss-of-function of U2A' causes lethality, demonstrating it is essential for U2 snRNP function. Importantly, U2A' does not require heterodimer formation with SNF for either its vital function or U2 snRNP assembly, indicating U2A' has an essential SNF/U2B"-independent function. |
Genetic loss-of-function (null alleles), in vivo co-immunoprecipitation, domain interaction mapping |
Nucleic acids research |
High |
11557816
|
| 2014 |
U2A' binds U2B" with nanomolar affinity but binds U1A with only micromolar affinity. There is RNA-dependent cooperativity (thermodynamic linkage) between protein-protein and protein-RNA binding in the U2A'/U2B"/U2 snRNA complex formation. This combination of tight binding and cooperativity ensures that the U2A'/U2B" complex is partitioned exclusively to the U2 snRNP. |
Fluorescence binding assays and isothermal titration calorimetry (ITC) measuring protein-protein and protein-RNA interactions |
Biochemistry |
High |
24866816
|
| 2015 |
All three RNA-binding site mutations of SmD3 were lethal in cells lacking the U2 snRNP subunit Lea1 (yeast U2A'), and benign C-terminal truncations of SmD3 were also lethal in the absence of Lea1. Conversely, SMD3-E35A specifically suppressed the temperature-sensitivity of lea1Δ. These genetic interactions place Lea1/U2A' in an epistatic network with Sm proteins at the U1/U2 snRNP interface. |
Genetic epistasis analysis via double-mutant combinations (synthetic lethality and suppression) in yeast |
RNA (New York, N.Y.) |
Medium |
25897024
|
| 2021 |
SNRPA1 interacts with a structural splicing enhancer (RNA structural element) enriched near cassette exons to promote cassette exon inclusion in a non-canonical, context-dependent manner. SNRPA1-mediated regulation of PLEC alternative splicing promotes cancer cell invasion and metastatic lung colonization. This noncanonical splicing enhancer role was established by loss-of-function experiments and splicing modulating morpholinos. |
SNRPA1 loss-of-function, RNA structural analysis, splicing assays, invasion/metastasis functional assays, morpholino rescue |
Science (New York, N.Y.) |
High |
33986153
|
| 2017 |
SNRPA1 physically interacts with SNRPD1 and PNN in human pluripotent stem cells, co-localizing with hPS spliceosomes. SNRPA1 depletion causes loss of pluripotency and blocks hiPS generation, and reduces hPS spliceosome assembly, defining a role for SNRPA1 in pluripotency-specific spliceosome assembly. |
Co-immunoprecipitation, co-localization imaging, shRNA knockdown with pluripotency and spliceosome assembly readouts |
Stem cell research |
Medium |
28595116
|
| 2020 |
SNRPA1 expression in hepatocellular carcinoma cells is stimulated by mTOR activation. Knockdown of SNRPA1 inhibited HCC cell proliferation and xenograft tumorigenesis, induced apoptosis, and altered expression of FGF2, AFP, β-catenin, Ki-67, cyclin B1, caspase 3, p53, and p21. |
shRNA knockdown, mTOR activation/inhibition, xenograft mouse model, microarray gene profiling, qPCR |
Bioscience reports |
Medium |
32420585
|
| 2026 |
METTL3 and IGF2BP2 stabilize SNRPA1 mRNA through m6A methylation modification. SNRPA1 protein interacts with TWIST1 in NSCLC cells (Co-IP), and TWIST1 overexpression attenuates SNRPA1 knockdown-induced suppression of proliferation/migration/invasion. In vivo, SNRPA1 overexpression rescued the anti-tumor effects of METTL3 depletion. |
RIP assay, dual-luciferase reporter assay, actinomycin D mRNA stability assay, Co-IP, xenograft and lung metastasis models |
Cytotechnology |
Medium |
41841152
|
| 2025 |
lncRNA ENST00000458139 (lnc458) physically interacts with SNRPA1 protein (identified by biotin-labeled RNA pulldown + mass spectrometry). SNRPA1 mediates MYC transactivation downstream of lnc458, leading to upregulation of DDIT4 and mitochondrial dysfunction/apoptosis in podocytes. |
Biotin-labeled RNA pulldown followed by mass spectrometry, RNA-seq, gain/loss-of-function |
International immunopharmacology |
Medium |
40680608
|
| 2026 |
SNRPA1 and DHM (dihydromethysticin) regulate c-MYC expression through affecting c-MYC protein stability. Downregulation of SNRPA1 by DHM increases c-MYC protein degradation, inhibiting Cr(VI)-induced cell transformation and cancer stemness properties. |
Western blot for c-MYC stability (CHX chase implied), knockdown/overexpression, soft agar colony formation, xenograft tumorigenesis |
Chemical research in toxicology |
Low |
42135982
|