AN ALTERED INTRACELLULAR-DISTRIBUTION OF THE AUTOANTIGEN LA SS-B WHENTRANSLATED FROM A LA MESSENGER-RNA ISOFORM

Transcription of the gene encoding for the nuclear autoantigen La resu lted in La mRNA isoforms. A promoter switching combined with an altern ative splicing pathway replaced exon 1 with exon 1'. Similar to mRNAs encoding for ribosomal proteins, exon 1' started with a pyrimidine-ric h 5'-terminus. Moreover, exon 1' contained 5'-GC-rich regions and an o ligo(U)tail of 23 uridine residues. Exon 1' encoded for three open rea ding frames upstream of the La protein reading frame. In spite of this unusual structure, exon 1' La mRNAs were translated not only in vitro but also in transiently transfected cells. The translational efficien cy of exon 1' La mRNA was about 14% of exon 1 La mRNA using rabbit ret iculolysate for in vitro translation. Finally, we established permanen tly transfected mouse cell lines expressing the human exon 1 or exon 1 ' La mRNA isoform. In all cell lines the respective La mRNAs were tran slated to La protein. The exon 1 La mRNA-expressing cell lines display ed a mostly nuclear staining pattern. In contrast, a major portion of La protein was found in the cytoplasm of cell lines expressing exon 1' La mRNA. (C) 1997 Academic Press.