Calreticulin binds hYRNA and the 52-kDa polypeptide component of the Ro/SS-A ribonucleoprotein autoantigen

Shih Tsung Cheng, Tho Q. Nguyen, Yih Sheng Yang, J. Donald Capra, Richard D. Sontheimer

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Abstract

Calreticulin (CR) is a multifunctional, calcium-binding protein that has recently been shown to bind to and promote the replication of the rubella virus genome in mammalian cells. While CR is now widely recognized as a new human autoantigen, the relationship between CR and the Ro/SS-A ribonucleoprotein (RNP) autoantigen has been somewhat controversial. In this work, we demonstrate that unphosphorylated human rCR binds specifically and distinctly to in vitro transcribed forms of hYRNA, the RNA backbone of the Ro/SS-A RNP particle. This interaction appears to be mediated by binding through the N- and C-terminal domains of CR, but not by the central proline- rich domain. Furthermore, our studies indicate that CR can facilitate the binding of the 60-kDa polypeptide component of the Ro/SS-A RNP (Ro60) to hYRNA. In addition, CR and the 52-kDa Ro/SS-A polypeptide (Ro52) appear to be capable of interacting through direct protein-protein binding. These studies confirm that CR is an hYRNA-binding protein, and provide for the first time a molecular mechanism by which Ro52 can be linked physically to hYRNA. Through these molecular interactions and its known functional role as a chaperone, it is suggested that CR plays a supportive role in the formation of the Ro/SS-A RNP complex. The capacity of CR to interact with RNA viruses such as rubella provides an additional argument for an infectious trigger for autoantibody production against self RNP particles such as Ro/SS-A.

Original languageEnglish (US)
Pages (from-to)4484-4491
Number of pages8
JournalJournal of Immunology
Volume156
Issue number11
StatePublished - Jun 1 1996

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Calreticulin
Ribonucleoproteins
Autoantigens
Peptides
Rubella virus
Calcium-Binding Proteins
Rubella
RNA Viruses
Proline
Protein Binding
Autoantibodies
Carrier Proteins
Genome
RNA

ASJC Scopus subject areas

  • Immunology

Cite this

Calreticulin binds hYRNA and the 52-kDa polypeptide component of the Ro/SS-A ribonucleoprotein autoantigen. / Cheng, Shih Tsung; Nguyen, Tho Q.; Yang, Yih Sheng; Capra, J. Donald; Sontheimer, Richard D.

In: Journal of Immunology, Vol. 156, No. 11, 01.06.1996, p. 4484-4491.

Research output: Contribution to journalArticle

Cheng, Shih Tsung ; Nguyen, Tho Q. ; Yang, Yih Sheng ; Capra, J. Donald ; Sontheimer, Richard D. / Calreticulin binds hYRNA and the 52-kDa polypeptide component of the Ro/SS-A ribonucleoprotein autoantigen. In: Journal of Immunology. 1996 ; Vol. 156, No. 11. pp. 4484-4491.
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AU - Capra, J. Donald

AU - Sontheimer, Richard D.

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