DOI Page / Citation link:
https://doi.org/10.11588/diglit.48120#0039
Abstracts
21
The TH Ribonucleoprotein Particle: Identity with RNase MRP and
Association with RNase P
H. Gold1, M. Bartkiewicz2, and J. Craft1
‘Yale University School of Medicine, New Haven, CT 06510, USA
2 Polish Academy of Sciences, Warsaw, Poland
Anti-Th antibodies, first described in two patients in 1982 and thougth to be
uncommon, immunoprecipitate a 7-2 RNA and an approximately 40 kilodalton
polypeptide of nucleolar origin. The RNase P RNP, comprised of a 400
nucleotide RNA and unknown polypeptide(s), is an endoribonuclease that pro-
cesses all precursor tRNAs to generate their mature 5' termini. We have shown
previously that anti-Th antibodies immunoprecipitate Hl RNA (the RNA compo-
nent of HeLa RNase P) from cell extracts (PNAS85: 5483, 1988), although no
structural relationship between these two RNPs has been identified.
Using immunoprecipitation of [32P]labeled HeLa cell extracts, we have now
identified 30 patients with anti-Th antibodies. All sera also immunoprecipitated
the RNase P particle from these extracts, strongly suggesting that these two par-
ticles share an immunogenic polypeptide(s) or are structurally associated. These
sera immunoprecipitated at least seven polypeptides from HeLa cell extracts la-
beled with [35S]methionine, with a polypeptide of approximately 38 kilodaltons
as a likely antigenic target.
The Th RNA from HeLa cells was sequenced and it was approximately 80%
homologous with murine RNase MRP RNA, suggesting that the Th RNP and
RNase MRP are identical. RNase MRP makes an endoribonucleolytic cleavage
in mitochondrial primer RNA which is believed to be involved in replication of
mitochondrial DNA. A sequence comparison of the Th and Hl RNAs showed
that although these RNAs are distinct, they do contain some small blocks of con-
served sequences which suggest a common binding site for an antigenic protein.
Of the 18 patients on whom clinical data were available, six had scleroderma
(SD), five had CREST, four had isolated Raynaud’s, two had primary biliary
cirrhosis, and one had SLE with longstanding Raynaud’s and telangiectasias. In
the patients with SD, diffuse skin disease occurred in only two and renal disease
in none.
These data indicate that the Th RNP and RNase MRP are the same and
physically related to RNase P RNP, and in the nucleolus, the Th RNP is likely
involved in RNA processing events. Like certain other autoantigenic RNPs, these
particles are constituted by several polypeptides which are most likely im-
munoprecipitated by their linkage on an RNA backbone. Although the frequency
of these antibodies is as yet unknown, they are not uncommon and they occur
predominantly in patients with SD and related diseases with relatively mild
clinical expression.
21
The TH Ribonucleoprotein Particle: Identity with RNase MRP and
Association with RNase P
H. Gold1, M. Bartkiewicz2, and J. Craft1
‘Yale University School of Medicine, New Haven, CT 06510, USA
2 Polish Academy of Sciences, Warsaw, Poland
Anti-Th antibodies, first described in two patients in 1982 and thougth to be
uncommon, immunoprecipitate a 7-2 RNA and an approximately 40 kilodalton
polypeptide of nucleolar origin. The RNase P RNP, comprised of a 400
nucleotide RNA and unknown polypeptide(s), is an endoribonuclease that pro-
cesses all precursor tRNAs to generate their mature 5' termini. We have shown
previously that anti-Th antibodies immunoprecipitate Hl RNA (the RNA compo-
nent of HeLa RNase P) from cell extracts (PNAS85: 5483, 1988), although no
structural relationship between these two RNPs has been identified.
Using immunoprecipitation of [32P]labeled HeLa cell extracts, we have now
identified 30 patients with anti-Th antibodies. All sera also immunoprecipitated
the RNase P particle from these extracts, strongly suggesting that these two par-
ticles share an immunogenic polypeptide(s) or are structurally associated. These
sera immunoprecipitated at least seven polypeptides from HeLa cell extracts la-
beled with [35S]methionine, with a polypeptide of approximately 38 kilodaltons
as a likely antigenic target.
The Th RNA from HeLa cells was sequenced and it was approximately 80%
homologous with murine RNase MRP RNA, suggesting that the Th RNP and
RNase MRP are identical. RNase MRP makes an endoribonucleolytic cleavage
in mitochondrial primer RNA which is believed to be involved in replication of
mitochondrial DNA. A sequence comparison of the Th and Hl RNAs showed
that although these RNAs are distinct, they do contain some small blocks of con-
served sequences which suggest a common binding site for an antigenic protein.
Of the 18 patients on whom clinical data were available, six had scleroderma
(SD), five had CREST, four had isolated Raynaud’s, two had primary biliary
cirrhosis, and one had SLE with longstanding Raynaud’s and telangiectasias. In
the patients with SD, diffuse skin disease occurred in only two and renal disease
in none.
These data indicate that the Th RNP and RNase MRP are the same and
physically related to RNase P RNP, and in the nucleolus, the Th RNP is likely
involved in RNA processing events. Like certain other autoantigenic RNPs, these
particles are constituted by several polypeptides which are most likely im-
munoprecipitated by their linkage on an RNA backbone. Although the frequency
of these antibodies is as yet unknown, they are not uncommon and they occur
predominantly in patients with SD and related diseases with relatively mild
clinical expression.