Binds to the 3' poly(U) terminii of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation.
We have tested the hypothesis that the mammalian La protein, which appears to be required for accurate and efficient RNA polymerase III transcription, is a transcription termination factor. Our data suggest that 3' foreshortened transcripts generated in La's absence are components of a novel transcription intermediate containing a paused polymerase. These transcripts are produced by fractionated transcription complexes, are synthesized with kinetics different from full-length transcripts, and are chasable to completion from the stalled transcription complexes. Together, these findings argue that termination by RNA polymerase III requires auxilliary factor(s) and implicate La as such a factor. Since La appears to facilitate transcript completion and release and also binds the resulting RNA product, it may be a regulator of RNA polymerase III transcription.
J. Biol. Chem. 263, 18043-18051 (1988)[PubMed:3192525]
La is an autoimmune RNA-binding protein of 47 kDa that plays a role in the transcription of RNA polymerase III. Both genomic and complementary DNAs were isolated that encompass the coding sequence of the human La molecule. The genomic clones encompass 11 exons and a putative G/C-rich promoter upstream of the mRNA start site. The cDNA sequence encodes a protein of 408 amino acids and can be divided into two structural domains based upon amino acid content and protease sensitivity. An unusually long stretch of 130 amino acids, much of which was predicted to form a stable alpha-helix, was found near the middle of the protein between the two domains. A ribonucleoprotein (RNP) consensus sequence was found just NH2-terminal to the long alpha-helix. The RNP consensus sequence is split into two exons by the fifth intron. Expression of three separate fragments of the La protein in Escherichia coli showed that a strongly autoimmune-reactive portion resides in the fragment containing the RNP consensus sequence and most of the long alpha-helical core. Autoantibodies from La patients also reacted with the terminal regions of the protein, but the extent of reactivity varied among patients. Differences in reactivity of autoantibodies to each portion of La protein may reflect an evolution of recognition of different epitopes during the development of the autoimmune response. These findings support an antigen-driven mechanism for autoimmune reactivity.
Interacting selectively and non-covalently with messenger RNA (mRNA), an intermediate molecule between DNA and protein. mRNA includes UTR and coding sequences, but does not contain introns.
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 three 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, crude S130 was fractionated by histone-agarose affinity chromatography. Two separate activities affecting the histone mRNA half-life were detected. The histone-agarose-bound fraction contained a histone mRNA destabilizer that was activated by histone proteins; the unbound fraction contained a histone mRNA stabilizer. Further chromatographic fractionation of unbound material revealed only a single protein stabilizer, which was purified to homogeneity, partially sequenced, and found to be La, a well-characterized RNA-binding protein. When purified La was added to reaction mixtures containing polysomes, a histone mRNA decay intermediate was stabilized. This intermediate corresponded to histone mRNA lacking 12 nucleotides from its 3' 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. We suggest that La prolongs the histone mRNA half-life during S phase and thereby increases histone protein production.
Interacting selectively and non-covalently with a nucleotide, any compound consisting of a nucleoside that is esterified with (ortho)phosphate or an oligophosphate at any hydroxyl group on the ribose or deoxyribose.
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. An opal suppressor tRNA served as a functional probe to examine the activities of yeast and human (h)La proteins in this process in fission yeast. An RNA recognition motif and Walker motif in the metazoan-specific C-terminal domain (CTD) of hLa maintain pre-tRNA in an unprocessed state by blocking the 5'-processing site, impeding an early step in the pathway. Faithful phosphorylation of hLa on serine 366 reverses this block and promotes tRNA maturation. The results suggest that regulation of tRNA maturation at the level of RNase P cleavage may occur via phosphorylation of serine 366 of hLa.
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 three 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, crude S130 was fractionated by histone-agarose affinity chromatography. Two separate activities affecting the histone mRNA half-life were detected. The histone-agarose-bound fraction contained a histone mRNA destabilizer that was activated by histone proteins; the unbound fraction contained a histone mRNA stabilizer. Further chromatographic fractionation of unbound material revealed only a single protein stabilizer, which was purified to homogeneity, partially sequenced, and found to be La, a well-characterized RNA-binding protein. When purified La was added to reaction mixtures containing polysomes, a histone mRNA decay intermediate was stabilized. This intermediate corresponded to histone mRNA lacking 12 nucleotides from its 3' 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. We suggest that La prolongs the histone mRNA half-life during S phase and thereby increases histone protein production.
The covalent alteration of one or more nucleotides within a tRNA molecule to produce a tRNA molecule with a sequence that differs from that coded genetically.
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. An opal suppressor tRNA served as a functional probe to examine the activities of yeast and human (h)La proteins in this process in fission yeast. An RNA recognition motif and Walker motif in the metazoan-specific C-terminal domain (CTD) of hLa maintain pre-tRNA in an unprocessed state by blocking the 5'-processing site, impeding an early step in the pathway. Faithful phosphorylation of hLa on serine 366 reverses this block and promotes tRNA maturation. The results suggest that regulation of tRNA maturation at the level of RNase P cleavage may occur via phosphorylation of serine 366 of hLa.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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