RNP Particles, Splicing and Autoimmune Diseases

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The first insights into the site and mechanisms of RNA process­ ing to functional mRNA in eukaryotic cells came from the group of Georgiev (Lukanidin et al. 1972) who demonstrated the association of rapidly labelled, heterogeneous nuclear RNA (hnRNA) with a limited number of specific proteins in the cell nucleus. These "informofers", i. e. packaged precursors of mRNA (pre-mRNA or hnRNA), are in a form presumably amenable to the action of nucleases. With the availability of better analytical techniques, the considerable heterogeneity of hnRNA associated proteins was revealed (Niessing and Sekeris 1970), suggesting a role that was more composite, rather than solely structural, for these proteins. Later studies investigated the RNA binding behavior of these proteins (Schenkel et al. 1988, 1989, Wilk et al. 1983). For a long time, the small nuclear RNAs, well characterized with respect to primary structure (reviewed by Reddy and Busch 1983), were naively ignored regarding their function. Several events then set the stage for a detailed study of the intricate mechanisms of the splicing process and other steps involved in hnRNA processing: (1) The demonstration of a second class of nuclear ribonucleoproteins (RNPs), composed of small nuclear RNAs (snRNAs) and another characteristic group ofheterogene­ ous proteins (Lerner et al. 1980, Guialis et al. 1983), (2) the detec­ tion of the association of snRNPs with hnRNPs by virtue of base pairing between hnRNA and snRNA (Flytzanis et al.