Disease relevance of Lsm2

• Autoantibodies directed at a diverse group of proteins of the U1/Sm ribonucleoprotein (snRNP) are characteristic of systemic lupus erythematosus and are found in the MRL murine model of this disease [1].

High impact information on Lsm2

• These results indicate that soluble cytosolic factors mediate the differential m3G-cap dependence of U1 and U2 snRNP nuclear import in somatic cells and oocytes [2].
• In vitro nuclear import of snRNPs: cytosolic factors mediate m3G-cap dependence of U1 and U2 snRNP transport [2].
• Interestingly, when the in vitro system was provided with cytosol from Xenopus oocytes instead of somatic cells, U1 and U2 snRNP nuclear import was provided with cytosol from Xenopus oocytes instead of somatic cells, U1 and U2 snRNP nuclear import was m3G-cap dependent [2].
• Histone RNA 3' end formation occurs through a specific cleavage reaction that requires, among other things, base-pairing interactions between a conserved spacer element in the pre-mRNA and the minor U7 snRNA present as U7 snRNP [3].
• Anti-small nuclear (sn)RNP antibodies, specific for determinants of the nucleoplasmic snRNP species containing U1, U2, U4, U5, and U6 RNAs, were found associated preferentially with perichromatin fibrils, interchromatin granules, and coiled bodies [4].

Biological context of Lsm2

• DNA sequence analysis of a segment of 15 kb, situated between G7b and G7a and present in the mouse but absent in human, revealed about 11 kb of DNA harboring a large number of repetitive sequences and 4 kb harboring a novel gene, G7e [5].
• The other two H2a genes are adjacent, with the 3' ends of their mRNAs separated by only 49 nucleotides in the DNA and the U7 snRNP binding sites separated by only 20 nucleotides [6].
• Newly synthesized snRNAs appear transiently in the cytoplasm where they assemble into ribonucleoprotein particles, the snRNP particles, before returning permanently to the interphase nucleus [7].
• SMN is involved in snRNP transport and nuclear RNA splicing, but axonal transport of SMN has also been shown to occur in motor neurons [8].

Anatomical context of Lsm2

• 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 [9].
• In this report, the cytoplasmic assembly of snRNP core particles in L929 mouse fibroblasts was investigated by kinetic analysis of assembly intermediates resolved on sucrose gradients [10].
• This study examines the role of transgenic B lymphocytes in the regulation of autoreactive T cells to the snRNP autoantigen [1].
• Nuclear matrix preparations that were digested with DNases and RNases showed that interphasic p255 still localized to nuclear speckles even though snRNA and snRNP antigens were removed [11].
• EM immunogold labeling confirmed the LM observations but additionally showed that snRNP content peaked in the nuclei of pachytene spermatocytes and that 2 cytoplasmic components found exclusively in meiotic and post-meiotic germ cells were intensively reactive [12].

Associations of Lsm2 with chemical compounds

• Kinetic studies, using the Sm antiserum to immunoprecipitate the methionine-labeled snRNP proteins, suggest that the B protein has a half-life of 90 to 120 min in the cytoplasm [7].

Other interactions of Lsm2

• Two other genes are located in this critical interval (G7b and G7a/Bat-6), and there might still be other undetected genes present in the region [13].
• The internal component of PI1 staining consisted of irregular patches and strands in the nucleoplasm, closely resembling snRNP staining as reported by others [14].
• These results indicate that p255 and SC-35 are present in the same nuclear structures, to which they are more tightly bound than the snRNP antigens [11].
• This degradation of a model 3' product by a 5'-3' exonuclease suggests a mechanism for the release of the U7 snRNP after processing by shortening the cut-off histone spacer sequences base paired to U7 RNA [15].
• Cytoplasmic assembly of snRNP core proteins from 6S and 20S SnRNA-free intermediates and nuclear exchange of the U1 and U2 snRNP specific proteins [16].

Analytical, diagnostic and therapeutic context of Lsm2

• Specific involvement of the U3 snRNP is demonstrated by native gel electrophoresis of the processing reaction followed by Northern blotting and by oligonucleotide-directed RNAase H abolition of processing activity [17].
• Localization was examined by in situ hybridization with U1, U2 and U6 riboprobes and immunofluorescence microscopy using a monoclonal antibody to snRNP antigens [18].
• Immunoprecipitation of gradient fractions with anti-snRNP autoimmune antisera identify pools of 6 and 20 S snRNA-free snRNP protein intermediates [10].
• The relative abundance of the snRNP B protein in the cytoplasm is determined by Western blotting with the Sm class of autoantibodies and is approximately 25% of the nuclear abundance [7].
• RT-PCR analysis indicates that the three isoforms are stable transcripts, all at low frequency when compared with SmX5 [19].

References