A possible role for the 60-kD Ro autoantigen in a discard pathway for defective 5S rRNA precursors.

O’Brien, Charles A.; Wolin, Sandra L.

doi:10.1101/gad.8.23.2891

Cited by 181 publications

(168 citation statements)

References 63 publications

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“…Like La, the human autoantigen Ro binds to pol III transcripts to form ribonucleoprotein particles. In the case of Ro, however, binding is specific for the pol III-transcribed Y RNAs and defective 5S rRNA molecules (39,40). The function of Ro is unclear, although the observation that it binds specifically to nonfunctional 5S transcripts suggests it may have a role in 5S rRNA quality control (40).…”

Section: The Human Autoantigen Ro Is Not Found Associated With Pol Iii-mentioning

confidence: 98%

Human La is found at RNA polymerase III-transcribed genes in vivo

Fairley

Kantidakis

Kenneth

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The human La autoantigen can bind to nascent RNA transcripts and has also been postulated to act as an RNA polymerase III (pol III) transcription initiation and termination factor. Here, we show by chromatin immunoprecipitation (ChIP) that La is associated with pol III-transcribed genes in vivo. In contrast, the Ro autoantigen, which can also bind pol III transcripts, is not found at these genes. The putative pol III transcription factors NF1 and TFIIA are also not detected at class III genes. Binding of La remains when transcription is repressed at mitosis and does not correlate with the presence of polymerase at the gene. However, gene occupancy depends on the phosphorylation status of La, with the less prevalent, unphosphorylated form being found selectively on pol III templates.La ͉ NF1 ͉ TFIIA ͉ chromatin immunoprecipitation ͉ RNA polymerase III transcription R NA polymerase III (pol III) is responsible for the production of a number of short, untranslated RNAs that are essential for cellular growth; pol III transcription is therefore a major determinant of the biosynthetic capacity of cells (reviewed in refs. 1 and 2). The key to understanding how this influence is regulated is the identification of factors that can control expression. Pol III promoters can be divided into three types that utilize different transcription factors for their activity. Type 1 and 2 promoters, exemplified by the 5S rRNA and tRNA promoters, respectively, recruit TFIIIA and͞or TFIIIC, through binding to sequence-specific elements within the gene (reviewed in refs. 3 and 4). TFIIIC in turn recruits a TFIIIB complex containing Brf1, TBP, and Bdp1, which is able to recruit the polymerase through protein-protein interactions. In contrast, type 3 promoters, such as that for U6 small nuclear RNA (snRNA), contain gene external elements that are recognized by the SNAPc complex and TFIIIB (4); however, the TFIIIB in this case differs from that used for type 1 and type 2 promoters in utilizing Brf2 instead of Brf1 (4, 5). In addition to these basal transcription factors, a number of other proteins have been found to influence pol III transcription in mammals. Some of these regulators have been shown to associate with pol III templates in vivo, including c-Myc (6), RB (7), ␤-actin (8), and the protein kinase CK2 (9, 10). However, there are a number of other proteins, including La, TFIIA and NF1, for which a role in pol III transcription has been suggested from experiments in vitro, but which has not been confirmed in vivo.The human autoantigen La is a highly abundant protein found associated with newly synthesized pol III products (11,12). La binds to nascent pol III transcripts through the UUU-OH at their 3Ј ends, which corresponds to the pol III termination signal, and also has affinity for their 5Ј ends (13-15). One of the functions of La is in the stabilization of these transcripts, which promotes their processing to the mature forms (16). However, La has also been reported to have effects on pol III transcription. Immunodepletion of La...

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Section: The Human Autoantigen Ro Is Not Found Associated With Pol Iii-mentioning

confidence: 98%

Human La is found at RNA polymerase III-transcribed genes in vivo

Fairley

Kantidakis

Kenneth

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…A molecular definition for these autoantigens has been provided by the isolation of cDNA clones (25,27). The 60-kDa SS-A/Ro protein binds to hY RNA in an in vitro reconstitution assay (25), and has been proposed to function as part of a novel quality control of discard pathway for 5S ribosomal RNA (28). Ro52, one of the components of the SS-A/Ro complex, includes two isoforms, 52-␣ and 52-␤.…”

Section: Discussionmentioning

confidence: 99%

SS-A/Ro52, an Autoantigen Involved in CD28-Mediated IL-2 Production

Ishii

Ohnuma

Murakami

et al. 2003

The Journal of Immunology

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An autoantibody against SS-A/Ro52 (Ro52) is most frequently found in the sera of patients with Sjögren’s syndrome, systemic lupus erythematosus, and congenital heart block from anti-Ro52 Ab-positive mother. However, the physiological function of the autoantigen SS-A/Ro52 has not yet been elucidated. In this study, we describe the role of Ro52 protein in T cell activation. Overexpression of SS-A/Ro52 in Jurkat T cell resulted in enhanced IL-2 production following CD28 stimulation. Furthermore, transfection of anti-Ro52-specific small RNA duplexes partially blocked the expression of native and overexpressed Ro52 in Jurkat T cell, resulting in decreased IL-2 production via CD28 pathway in these cells. Finally, intracellular localization of Ro52 dramatically changed following CD28 stimulation. Our data reveal a novel function of Ro52 in CD28-mediated pathway, which eventually contributes to cytokine production and expression of the T cell biological programs.

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“…The mutant RNAs are processed inefficiently to mature 5S RNA. They are less stable than the wild-type 5S RNA precursors and eventually degrade (O'Brien and Wolin, 1994). The Ro protein binds 5S RNA precursors containing a variety of internal mutations while discriminating against the wild-type 5S RNA.…”

Section: Genome Research 139mentioning

confidence: 99%

“…In Xenopus, a well-characterized model, there is a developmental regulation of expression for the two families of 5S rRNA (Peterson et al 1980). O'Brien and Wolin (1994) have shown that the Ro protein binds specifically some mutant 5S RNA, and this protein has been proposed to function in a quality control or discard pathway for 5S rRNA synthesis in Xenopus oocytes (Shi et al 1996).…”

mentioning

confidence: 99%

Analysis of the 5S RNA Pool in Arabidopsis thaliana: RNAs Are Heterogeneous and Only Two of the Genomic 5S Loci Produce Mature 5S RNA

Cloix¹,

Tutois²,

Yukawa³

et al. 2001

Genome Res.

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One major 5S RNA, 120 bases long, was revealed by an analysis of mature 5S RNA from tissues, developmental stages, and polysomes in Arabidopsis thaliana. Minor 5S RNA were also found, varying from the major one by one or two base substitutions; 5S rDNA units from each 5S array of the Arabidopsis genome were isolated by PCR using CIC yeast artificial chromosomes (YACs) mapped on the different loci. By using a comparison of the 5S DNA and RNA sequences, we could show that both major and minor 5S transcripts come from only two of the genomic 5S loci: chromosome 4 and chromosome 5 major block. Other 5S loci are either not transcribed or produce rapidly degraded 5S transcripts. Analysis of the 5Ј-and 3Ј-DNA flanking sequence has permitted the definition of specific signatures for each 5S rDNA array.

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A possible role for the 60-kD Ro autoantigen in a discard pathway for defective 5S rRNA precursors.

Cited by 181 publications

References 63 publications

Human La is found at RNA polymerase III-transcribed genes in vivo

Human La is found at RNA polymerase III-transcribed genes in vivo

SS-A/Ro52, an Autoantigen Involved in CD28-Mediated IL-2 Production

Analysis of the 5S RNA Pool in Arabidopsis thaliana: RNAs Are Heterogeneous and Only Two of the Genomic 5S Loci Produce Mature 5S RNA

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