Disease relevance of Snrpa

• Mice with severe combined immunodeficiency were reconstituted with H1A and U1A before infection with L. major [1].
• In human immunodeficiency virus type 1 (HIV-1) the promoter-proximal poly(A) site is blocked by interaction of U1 snRNP with the closely positioned major splice donor site (MSD) 200 nucleotides downstream [2].
• The U1 snRNP-specific 70-kD peptide was found to be the most prominent RNP antigen recognized by high-titre anti-RNP sera, mainly found in patients with mixed connective tissue disease (MCTD) [3].
• The monoclonal antibody 2.73 was derived from the lupus prone MRL/n line and is reactive with the 70K protein of the U1 snRNP particle [4].

High impact information on Snrpa

• Thus, U1A protein regulates the production of its own mRNA via a mechanism that involves pre-mRNA binding and inhibition of polyadenylation [5].
• The U1-snRNP-associated phosphoprotein complex is immunoprecipitated by monoclonal antibodies reactive with serine/arginine (SR) proteins that comprise a structurally related family of splicing factors [6].
• The phosphorylation and/or recruitment of these proteins to the U1-snRNP complex is induced by multiple apoptotic stimuli (e.g., Fas ligation, gamma irradiation, or UV irradiation), and is blocked by overexpression of bcl-2 [6].
• The association of phosphorylated SR proteins with the U1-snRNP complex in cells undergoing apoptosis suggests a mechanism for regulation of alternative splicing of apoptotic effector molecules [6].
• Surprisingly, the signal requirement for nuclear transport of U1 snRNP was found to differ between oocytes and somatic cells from mouse, monkey and Xenopus, in that the m3GGpppG-cap is no longer an essential signaling component in somatic cells [7].

Chemical compound and disease context of Snrpa

• Immunoreactivity between a monoclonal lupus autoantibody and the arginine/aspartic acid repeats within the U1-snRNP 70K autoantigen is conformationally restricted [8].

Biological context of Snrpa

• Nuclear transport of U1 snRNP in somatic cells: differences in signal requirement compared with Xenopus laevis oocytes [7].
• However, as shown by investigation of the transport kinetics of m3GpppG- and ApppG-capped U1 snRNPs, the m3GpppG-cap accelerates the rate of U1 snRNP import significantly indicating that it has retained a signaling role for nuclear targeting of U1 snRNP in somatic cells [7].
• Neutralization of IFN-gamma in H1A-reconstituted mice and IL-4 in U1A-reconstituted mice reversed the disease phenotype mediated by the two cell lines [1].
• We have studied the accumulation and localization of U1 RNA during mouse embryo development by in situ hybridization with a U1 RNA probe and immunofluorescence microscopy using a mouse monoclonal antibody to U1 snRNP [9].
• The U1 snRNP is involved in pre-mRNA splicing by defining introns and exons and by binding to consensus sequences within the pre-mRNA [10].

Anatomical context of Snrpa

• Undifferentiated B cells have more total U1A than differentiated cells and a greater proportion of this is not associated with the U1snRNP [11].
• However, when such mice were coimmunized with self snRNPs in conjunction with the human (foreign) U1 snRNP A protein, they developed autoantibodies directed against individual proteins of the U1 snRNP, in addition to anti-A antibodies; we have previously shown that such mice develop snRNP-specific, autoreactive T cells [12].
• In contrast, the ability of mutant pores to import ribosomal protein L23a and spliceosome protein U1A appeared intact [13].
• Our results suggest further that the binding of protein A to the U1 snRNP particle should be independent of proteins 70k and C. Mouse cells contain two U1 RNA species, U1a and U1b, which differ in the structure of stem/loop B, with U1a exhibiting the same stem/loop B sequence as U1 RNA from HeLa cells [14].
• These data suggest that the MAb 12E12 epitope is masked when U1A is prepared in reticulocyte lysate [15].

Associations of Snrpa with chemical compounds

• U1 snRNP and the splicing factor U2AF closely co-localize in the nucleus, both before and after actinomycin D treatment, suggesting that they may both be part of the same complex in vivo [16].
• U1A is a component of the uracil-rich small nuclear ribonucleoprotein [17].
• Quantitative densitometry of immunoprecipitated stable nuclear snRNPs labeled with [35S] methionine corrected for the published methionine content of the A, B, C, D, and E proteins indicates that the mature nuclear U1 snRNP probably contains four copies of D, two copies each of B, C, and A, and one copy of E [18].
• Moreover, the inhibition of protein synthesis by cycloheximide caused a superinduction in the amounts of the U1-snRNP-specific 70K transcripts [19].
• Several months after immunization, all mice treated with U1A-pulsed BMDCs did develop IgG, but not the complement C3 deposit in the glomeruli [20].

Other interactions of Snrpa

• U1 snRNP species were obtained which were selectively depleted of either protein C, A, C and A, or of all three U1-specific proteins C, A and 70k while retaining the common proteins B' to G [14].

Analytical, diagnostic and therapeutic context of Snrpa

• Immunoprecipitations of nuclear and cytoplasmic fractions after a pulse label and chase indicate that the snRNP D, E, F, and G proteins assemble first, followed by the small nuclear RNA (snRNA), then the snRNP B protein and, in the case of the U1 snRNP, the A and C proteins [18].
• Similar results were obtained for the distribution of the U1 snRNP as assayed by immunofluorescence microscopy: U1 RNA is predominantly localized in all nuclei except polar body nuclei [9].
• The results showed that BMDCs pulsed with U1A proteins by intravenous injection into BALB/c (H-2d) and DBA-2xNZW F1 (H-2d/u) mice were capable of activating the autoreactive T cells and inducing a high titre of immunoglobulin G (IgG) anti-U1A antibodies [20].
• Partially purified U1-snRNP from embryoid bodies was also obtained by elution from a DEAE-Sepharose column at around 0.18 M NH4Cl or by fractionation by 5-20% linear sucrose gradient centrifugation [21].

References