U3 snoRNP associates with fibrillarin a component of the scleroderma clumpy nucleolar domain

Abstract

Serum from patients with scleroderma recognizes the clumpy autoantigen. The present studies addressed the issue as to whether the clumpy nucleolar autoantigen recognized by scleroderma serum is fibrillarin-U3 snoRNP. Clones encoding for clumpy autoantigen were immunodetected from a lambdagt11 HeLa cell random-primed library with the serum from a patient with diffuse scleroderma and autoautoantibodies against clumpy autoantigen. Sequences from the recombinant phages were amplified by PCR and subcloned into a pCRII vector. The DNA was sequenced by a dideoxy termination reaction. Ten lambdagt11 clumpy clones were detected by immunoscreening. One containing the glycine-rich and RNP2 fibrillarin domains was expressed in lysogenic bacteria. The recombinant proteins were used to elicit antibodies in rabbits, and these exhibited clumpy nucleolar reactivity. The recombinant fibrillarin tested by ELISA was recognized by the clumpy scleroderma serum from the majority of patients. In situ hybridization assays showed that the fibrillarin tagged by the elicited antibodies was colocalized with U3 snoRNP in the nucleolus in a clumpy manner and coprecipitated the U3 snoRNP. In conclusion, the fibrillarin-U3 snoRNP complex is the major component of the clumpy subcellular domain. Therefore these molecules constitute an important target of scleroderma autoantibodies.

ISG20 promotes local tumor immunity and contributes to poor survival in human glioma

“…26 PML-NB is reported to be extensively involved in oncogenesis and gene transcription, [27][28][29] and the function differs according to its binding protein. [30][31][32][33] The endogenous ISG20 protein is present both in the nucleolus and in the Cajal bodies, and participates in the maturation of small nucleolar RNAs and ribosomal RNAs, and in ribosome biogenesis, [34][35][36][37][38][39] leading to the control of RNA stability. 40,41 ISG20 can be induced by type I and type II IFNs, 42,43 and its expression has been shown to be elevated during infection [44][45][46] and in several types of cancers.…”

The expression of Scratch genes in the developing and adult brain

“…First described as accessory bodies of the nucleolus [Cajal, 1903], the CBs now appear as a traffic area necessary for the maturation of snoRNAs before their nucleolar translocation. In particular, the U3 snoRNA synthesized in the nucleoplasm is 3′‐end processed by an unknown exonuclease within the CBs before association with the common snoRNA binding protein, fibrillarin [Herrera‐Esparza et al, 2002; Verheggen et al, 2002]. Then, the mature U3 snoRNPs are imported to the nucleoli where they act as guide RNAs in pre‐rRNA cleavage during ribosome biogenesis [Gerbi and Borovjagin, 1997; Scheer and Hock, 1999; Dragon et al, 2002; Verheggen et al, 2002; Carmo‐Fonseca, 2002b].…”

High-resolution microscopy of active ribosomal genes and key members of the rRNA processing machinery inside nucleolus-like bodies of fully-grown mouse oocytes

“…excision of the 5'ETS leading end of the pre-rRNA transcripts and in rRNA methylation [17,42]. Moreover, U3 snoRNA/fibrillarin sites well coincide with 47S precursor rRNA ( Fig.…”