Alternative titles; symbols
HGNC Approved Gene Symbol: SSB
Cytogenetic location: 2q31.1 Genomic coordinates (GRCh38) : 2:169,798,871-169,812,064 (from NCBI)
La is involved in diverse aspects of RNA metabolism, including binding and protecting 3-prime UUU(OH) elements of newly RNA polymerase III (see 606007)-transcribed RNA, processing 5-prime and 3-prime ends of pre-tRNA precursors, acting as an RNA chaperone, and binding viral RNAs associated with hepatitis C virus. La protein was originally defined by its reactivity with autoantibodies from patients with Sjogren syndrome (270150) and systemic lupus erythematosus (SLE; 152700) (Teplova et al., 2006).
Chambers et al. (1988) determined the amino acid sequence of the La protein. The cDNA sequence encodes a protein of 408 amino acids. By immunoprecipitation and immunoblotting, it appears to be a single phosphoprotein of 46 to 50 kD. Chambers et al. (1988) also identified at least 3 antigenic epitopes on the La protein and predicted regions of the protein involved in RNA binding based on structural similarities with other RNA-binding proteins. See Bini et al. (1990).
Grolz and Bachmann (1997) stated that there are 3 La pseudogenes. They also found that alternative splicing gives rise to 3 different mRNAs, all of which were expressed in all tissues tested, and all of which were translated into nuclear La protein in transfected mouse cells.
Histone mRNA is destabilized at the end of S phase and in cell-free mRNA decay reaction mixtures supplemented with histone proteins, indicating that histones might autoregulate the histone mRNA half-life. Histone mRNA destabilization in vitro requires 3 components: polysomes, histones, and postpolysomal supernatant (S130). Polysomes are the source of the mRNA and mRNA-degrading enzymes. To investigate the role of the S130 in autoregulation, McLaren et al. (1997) fractionated crude S130 by histone-agarose affinity chromatography. They detected 2 separate activities affecting the histone mRNA half-life. The histone-agarose-bound fraction contained a histone mRNA destabilizer that was activated by histone proteins; the unbound fraction contained a histone mRNA stabilizer. The authors performed further chromatographic fractionation of the unbound material, which revealed only a single, approximately 52-kD stabilizer protein. McLaren et al. (1997) purified this stabilizer to homogeneity, partially sequenced it, and identified it as La. Addition of purified La to reaction mixtures containing polysomes resulted in the stabilization of a histone mRNA decay intermediate. This intermediate corresponded to histone mRNA lacking 12 nucleotides from its 3-prime end and containing an intact coding region. Anti-La antibody blocked the stabilization effect. La had little or no effect on several other cell cycle-regulated mRNAs. McLaren et al. (1997) suggested that La prolongs the histone mRNA half-life during S phase and thereby increases histone protein production.
Conversion of a nascent precursor tRNA to a mature functional species is a multipartite process that involves the sequential actions of several processing and modifying enzymes. La is the first protein to interact with pre-tRNAs in eukaryotes. Intine et al. (2000) used an opal suppressor tRNA as a functional probe to examine the activities of yeast and human La proteins in this process in fission yeast. They found that an RNA recognition motif and Walker motif in the metazoan-specific C-terminal domain of human La maintain pre-tRNA in an unprocessed state by blocking the 5-prime-processing site, impeding an early step in the pathway. Faithful phosphorylation of human La on ser366 reverses this block and promotes tRNA maturation. The results suggested that regulation of tRNA maturation at the level of RNase P cleavage may occur via phosphorylation of ser366 of human La.
Teplova et al. (2006) reported the 1.85-angstrom crystal structure of the La N-terminal domain bound to a synthetic RNA with a UUU(OH) 3-prime end.
Chambers et al. (1988) determined that the La gene contains 11 exons.
By in situ hybridization and by screening a chromosome-specific library, Chambers et al. (1988) mapped the SSB gene to chromosome 2.
Bini, P., Chu, J.-L., Okolo, C., Elkon, K. Analysis of autoantibodies to recombinant La (SS-B) peptides in systemic lupus erythematosus and primary Sjogren's syndrome. J. Clin. Invest. 85: 325-333, 1990. [PubMed: 1688881] [Full Text: https://doi.org/10.1172/JCI114441]
Chambers, J. C., Kenan, D., Martin, B. J., Keene, J. D. Genomic structure and amino acid sequence domains of the human La autoantigen. J. Biol. Chem. 263: 18043-18051, 1988. [PubMed: 3192525]
Grolz, D., Bachmann, M. The nuclear autoantigen La/SS-associated antigen B: one gene, three functional mRNAs. Biochem. J. 323: 151-158, 1997. [PubMed: 9173875] [Full Text: https://doi.org/10.1042/bj3230151]
Intine, R. V. A., Sakulich, A. L., Koduru, S. B., Huang, Y., Pierstorff, E., Goodier, J. L., Phan, L., Maraia, R. J. Control of transfer RNA maturation by phosphorylation of the human La antigen on serine 366. Molec. Cell 6: 339-348, 2000. [PubMed: 10983981] [Full Text: https://doi.org/10.1016/s1097-2765(00)00034-4]
McLaren, R. S., Caruccio, N., Ross, J. Human La protein: a stabilizer of histone mRNA. Molec. Cell. Biol. 17: 3028-3036, 1997. [PubMed: 9154801] [Full Text: https://doi.org/10.1128/MCB.17.6.3028]
Teplova, M., Yuan, Y.-R., Phan, A. T., Malinina, L., Ilin, S., Teplov, A., Patel, D. J. Structural basis for recognition and sequestration of UUU(OH) 3-prime temini (sic) of nascent RNA polymerase III transcripts by La, a rheumatic disease autoantigen. Molec. Cell 21: 75-85, 2006. [PubMed: 16387655] [Full Text: https://doi.org/10.1016/j.molcel.2005.10.027]