Structure and function of La and Ro RNPs

Venrooij, W.J. van; Slobbe, Rob; Pruijn, Ger J. M.

doi:10.1007/bf00986765

Cited by 77 publications

(53 citation statements)

References 66 publications

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“…The RNA backbone of Ro RNP complexes is a Y RNA molecule, of which four have been identified in humans: hY1 (112 nts), hY3 (101 nts), hY4 (93 nts) and hY5 (84 nts). 79 The hY RNA molecules, which are all RNA polymerase III transcripts, are characterized by an oligouridylate stretch at the 3'-end to which the La protein is bound and a conserved stem structure formed by extensive base-pairing between the evolutionarily conserved 5' and 3' ends, which is the binding site of Ro60. 79 In contrast to the protein components of the Ro RNP complex, autoantibodies recognizing hY RNAs are restricted to hY5 RNA.…”

Section: The Ro Rnp Complex As Antigen In Sle and Sjsmentioning

confidence: 99%

“…79 The hY RNA molecules, which are all RNA polymerase III transcripts, are characterized by an oligouridylate stretch at the 3'-end to which the La protein is bound and a conserved stem structure formed by extensive base-pairing between the evolutionarily conserved 5' and 3' ends, which is the binding site of Ro60. 79 In contrast to the protein components of the Ro RNP complex, autoantibodies recognizing hY RNAs are restricted to hY5 RNA. 80 It has been shown recently that La is cleaved by granzyme B, 14 and that the protein is rapidly dephosphorylated and partly cleaved during apoptosis.…”

Section: The Ro Rnp Complex As Antigen In Sle and Sjsmentioning

confidence: 99%

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Caspase-dependent cleavage of nucleic acids

et al. 2000

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Autoimmune diseases are frequently characterized by the presence of autoantibodies directed against nucleic acidprotein complexes present in the nucleus of the cell. The mechanisms by which these autoantigenic molecules escape immunological tolerance are largely unknown, although a number of recent observations suggest that modified selfproteins generated during apoptosis may play an important role in the development of autoimmunity. It has been hypothesized that the recognition of these modified selfproteins by the immune system may promote autoantibody production. While apoptosis is specifically characterized by posttranslational modification of proteins, recent findings also show that nucleic acids are modified. This review summarizes the specific cleavages of some of these key nucleic acids, i.e. chromosomal DNA, ribosomal RNA and small structural RNAs (U1 snRNA, Y RNA), in apoptotic cells.

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Section: The Ro Rnp Complex As Antigen In Sle and Sjsmentioning

confidence: 99%

Section: The Ro Rnp Complex As Antigen In Sle and Sjsmentioning

confidence: 99%

Caspase-dependent cleavage of nucleic acids

et al. 2000

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“…Due to the presence of protease-sensitive PEST-regions [2], an affinity-purified recombinant human La protein preparation mostly contains the well-known N-terminal 29 kDa and the C-terminal 24 kDa domains of the La protein in addition to the full-length La protein. Both La fragments react with patient anti-La antibody ( Figure 1C, lane g), although with this particular patient serum (Ma) [6] the reactivity to the C-terminus was less intensive ( …”

Section: Development Of Anti-la Mab La4b6mentioning

confidence: 99%

“…One of the targets of these autoantibodies is the La/SS-B antigen, a protein with a molecular weight of about 47-kD [1,2]. In the nucleus the La protein may function as a transcription termination factor of RNA polymerase III [3,4].…”

Section: Introductionmentioning

confidence: 99%

Activation of a murine autoreactive B cell by immunization with human recombinant autoantigen La/SS-B: Characterization of the autoepitope

Tröster

Bartsch

Klein

et al. 1995

Journal of Autoimmunity

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Immunization of Balb/c mice with a homogeneously purified recombinant human La/SS-B protein resulted in activation of an autoreactive B cell secreting a novel monoclonal anti-La antibody termed La4B6. La4B6 reacted with La protein from a variety of sources including human, bovine, rat and mouse. ATP blocked the binding of La4B6 to recombinant La protein. The human epitope was identified as consisting of the amino acid sequence SKGRRFKGKGKGN, which includes the proposed ATP-binding site of the La protein. In the human and bovine La protein, the epitope exists as a continuous amino acid sequence. In rat and mouse the epitope was found to consist of the :amino acid sequence SKG interrupted by a species-specific insert of 16 amino acids, and followed by the second half of the epitope, the amino acid sequence RRFKGKGKGN. Our data suggest that in the case of the rat and mouse La proteins the two separated parts of the epitope are able to form a conformational epitope which looks similar to the continuous human epitope.

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“…La (also referred to as SS-B; (Wolin and Cedervall, 2002)) is a multifunctional phosphoprotein which has first been identified as an autoantigen in patients suffering from rheumatic diseases known as systemic lupus erythematosus or Sjogren's syndrome (van Venrooij et al, 1993). La homologues have since been identified in a variety of insect, yeast, and mammalian species (Bai et al, 1994;Chan et al, 1989;Pardigon and Strauss, 1996;Scherly et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Novel CNBP‐ and La‐based translation control systems for mammalian cells

Schlatter

Fussenegger²

2002

Biotech & Bioengineering

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Throughout the development of Xenopus, production of ribosomal proteins (rp) is regulated at the translational level. Translation control is mediated by a terminal oligopyrimidine element (TOP) present in the 5Ј untranslated region (UTR) of rp-encoding mRNAs. TOP elements adopt a specific secondary structure that prevents ribosome-binding and translation-initiation of rpencoding mRNAs. However, binding of CNBP (cellular nucleic acid binding protein) or La proteins to the TOP hairpin structure abolishes the TOP-mediated transcription block and induces rp production. Based on the specific CNBP-TOP/La-TOP interactions we have designed a translation control system (TCS) for conditional as well as adjustable translation of desired transgene mRNAs in mammalian cells. The generic TCS configuration consists of a plasmid encoding CNBP or La under control of the tetracycline-responsive expression system (TET OFF ) and a target expression vector containing a TOP module between a constitutive P SV40 promoter and the human model product gene SEAP (human secreted alkaline phosphatase) (P SV40 -TOP-SEAP-pA). The TCS technology showed excellent SEAP regulation profiles in transgenic Chinese hamster ovary (CHO) cells. Alternatively to CNBP and La, TOP-mediated translation control can also be adjusted by artificial phosphorothioate anti-TOP oligodeoxynucleotides. Confocal laser-scanning microscopy demonstrated cellular uptake of FITC-labeled oligodeoxynucleotides and their localization in perinuclear organelles within 24 hours. Besides their TOP-based translation-controlling capacity, CNBP and La were also shown to increase cap-independent translation from polioviral internal ribosomal entry sites (IRES) and La alone to boost cap-dependent translation initiation. CNBP and La exemplify for the first time the potential of RNAbinding proteins to exert translation control of desired transgenes and to increase heterologous protein production in mammalian cells. We expect both of these assets to advance current gene therapy and biopharmaceutical manufacturing strategies.

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Structure and function of La and Ro RNPs

Cited by 77 publications

References 66 publications

Caspase-dependent cleavage of nucleic acids

Caspase-dependent cleavage of nucleic acids

Activation of a murine autoreactive B cell by immunization with human recombinant autoantigen La/SS-B: Characterization of the autoepitope

Novel CNBP‐ and La‐based translation control systems for mammalian cells

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