Identity of the RNase MRP– and RNase P–associated Th/To autoantigen

Eenennaam, Hans van; Vogelzangs, Judith; Lugtenberg, Dorien; Hoogen, F.H.J. van den; Venrooij, Walther J. van; Pruijn, Ger J. M.

doi:10.1002/art.10673

Cited by 56 publications

(48 citation statements)

References 27 publications

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“…For most of these proteins, coimmunoprecipitation experiments demonstrated that they are, indeed, associated with both RNase MRP RNA and RNase P RNA in human cell lines (Pluk et al 1999;van Eenennaam et al 2002). Moreover, all 10 proteins copurified with catalytically active RNase P, suggesting that they are part of the core structure of the holoenzyme.…”

Section: Discussionmentioning

confidence: 98%

“…Surprisingly, Rpp25 and Rpp20 were not detected at all in 60-80S fractions, even though they have been demonstrated to be stably associated with RNase MRP (van Eenennaam et al 2002). Rpp25 and Rpp20 are evolutionarily related proteins, both belonging to the Alba superfamily (Aravind et al 2003), which directly bind to each other (Welting et al 2004) and most likely bind as a heterodimer to the P3 domain of RNase MRP RNA (Pluk et al 1999;van Eenennaam et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Rpp25 and Rpp20 are evolutionarily related proteins, both belonging to the Alba superfamily (Aravind et al 2003), which directly bind to each other (Welting et al 2004) and most likely bind as a heterodimer to the P3 domain of RNase MRP RNA (Pluk et al 1999;van Eenennaam et al 2002). In RNase MRP RNA, this region is in close proximity to nucleotides 68-71 and the P4 stem, which are believed to be part of the catalytic center of the enzyme.…”

Section: Discussionmentioning

confidence: 99%

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Differential association of protein subunits with the human RNase MRP and RNase P complexes

Welting¹,

Kikkert²,

Venrooij³

et al. 2006

RNA

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RNase MRP is a eukaryotic endoribonuclease involved in nucleolar and mitochondrial RNA processing events. RNase MRP is a ribonucleoprotein particle, which is structurally related to RNase P, an endoribonuclease involved in pre-tRNA processing. Most of the protein components of RNase MRP have been reported to be associated with RNase P as well. In this study we determined the association of these protein subunits with the human RNase MRP and RNase P particles by glycerol gradient sedimentation and coimmunoprecipitation. In agreement with previous studies, RNase MRP sedimented at 12S and 60-80S. In contrast, only a single major peak was observed for RNase P at 12S. The analysis of individual protein subunits revealed that hPop4 (also known as Rpp29), Rpp21, Rpp20, and Rpp25 only sedimented in 12S fractions, whereas hPop1, Rpp40, Rpp38, and Rpp30 were also found in 60-80S fractions. In agreement with their cosedimentation with RNase P RNA in the 12S peak, coimmunoprecipitation with VSV-epitope-tagged protein subunits revealed that hPop4, Rpp21, and in addition Rpp14 preferentially associate with RNase P. These data show that hPop4, Rpp21, and Rpp14 may not be associated with RNase MRP. Furthermore, Rpp20 and Rpp25 appear to be associated with only a subset of RNase MRP particles, in contrast to hPop1, Rpp40, Rpp38, and Rpp30 (and possibly also hPop5), which are probably associated with all RNase MRP complexes. Our data are consistent with a transient association of Rpp20 and Rpp25 with RNase MRP, which may be inversely correlated to its involvement in pre-rRNA processing.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differential association of protein subunits with the human RNase MRP and RNase P complexes

Welting¹,

Kikkert²,

Venrooij³

et al. 2006

RNA

Self Cite

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“…Later, it has been shown that this antibody directs against subunits of mitochondrial RNA processing and ribonuclease P complexes 32 . Of at least 6 subunits consisting of these complexes, a 120-kDa protein contains the major autoantibody epitope Anti-PM-Scl antibody produces a homogenous nucleolar pattern, and is rarely found in non-Caucasian patients 36 .…”

Section: Anti-th/to Antibodymentioning

confidence: 99%

Circulating Anti-Nuclear Antibodies in Systemic Sclerosis: Utility in Diagnosis and Disease Subsetting

Kuwana

2017

J Nippon Med Sch

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The presence of circulating anti-nuclear antibodies (ANAs) is a hallmark of immune dysregulation in patients with systemic sclerosis (SSc). Currently, a variety of SSc-specific ANAs, including anticentromere, anti-topoisomerase I, and anti-RNA polymerase III antibodies, have been well characterized, and their commercial kits are available worldwide. Since these autoantibodies are specifically detected in SSc patients and are associated with unique sets of disease manifestations, they are widely used in routine clinical practice for diagnosis, clinical subgrouping, and prediction of future organ involvements and prognosis. In addition, SSc-specific ANAs are also useful in predicting future development of SSc in patients with Raynaud's phenomenon without any scleroderma skin changes, because their production often precedes onset of SSc symptoms. Application of circulating SSc-specific ANA measurement to clinical practice has greatly improved patient care, but utility of the autoantibody testing could be maximized by combining other clinical information, such as degree and extent of skin thickness and disease duration. (J Nippon Med Sch 2017; 84: 56 63)

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“…Components of the ribonuclease MRP and ribonuclease P complexes are targeted by anti-Th/To antibodies [59]. They are present in a minority of patients with SSc (2-5 %) and seem to characterize a novel subset of patients with limited skin involvement (similar to ACA) but high risk for severe organ involvement and worse prognosis [17,42,60].…”

Section: Anti-th/to Antibodiesmentioning

confidence: 99%

Autoantikörper bei systemischer Sklerodermie: Bedeutung für Diagnostik, Prognose und Pathogenese

Grassegger¹,

Pohla‐Gubo

Frauscher

et al. 2008

Wien Med Wochenschr

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Systemic sclerosis is a generalized autoimmune connective tissue disease of unknown aetiology. Profound vascular and immunological dysregulations result in tissue fibrosis affecting the skin and internal organs. Currently, two main clinical subtypes are distinguished, i.e. limited and diffuse cutaneous systemic sclerosis, which differ significantly in the clinical course and prognosis. Autoantibodies against topoisomerase (Scl-70), centromere-associated proteins, and nucleolar antigens are important for the diagnosis of the disease and give clues for its clinical manifestations and prognosis (prognostic autoantibodies). For most of these antibodies, however, the role in pathogenesis is not established. Anti-centromere antibodies are associated with limited cutaneous involvement and risk for pulmonary hypertension, whereas anti-topoisomerase I is associated with diffuse progressive disease and severe interstitial lung disease. Anti-Th/To positivity is associated with limited skin involvement but a high risk for severe internal organ involvement (Kidneys, PAH, Lung fibrosis). Anti-RNA polymerase I/III antibodies are associated with a high risk for renal involvement. Autoantibodies against the PDGF receptor and fibrillin-1 seem to play important roles in the pathogenetic process of systemic sclerosis.

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Identity of the RNase MRP– and RNase P–associated Th/To autoantigen

Cited by 56 publications

References 27 publications

Differential association of protein subunits with the human RNase MRP and RNase P complexes

Differential association of protein subunits with the human RNase MRP and RNase P complexes

Circulating Anti-Nuclear Antibodies in Systemic Sclerosis: Utility in Diagnosis and Disease Subsetting

Autoantikörper bei systemischer Sklerodermie: Bedeutung für Diagnostik, Prognose und Pathogenese

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