An Altered Intracellular Distribution of the Autoantigen La/SS-B When Translated from a La mRNA Isoform☆

Abstract Transcription of the gene encoding for the nuclear autoantigen La resulted in La mRNA isoforms. A promoter switching combined with an alternative splicing pathway replaced exon 1 with exon 1′. Similar to mRNAs encoding for ribosomal proteins, exon 1′ started with a pyrimidine-rich 5′-terminus. Moreover, exon 1′ contained 5′-GC-rich regions and an oligo(U)-tail of 23 uridine residues. Exon 1′ encoded for three open reading 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 efficiency of exon 1′ La mRNA was about 14% of exon 1 La mRNA using rabbit reticulolysate for in vitro translation. Finally, we established permanently transfected mouse cell lines expressing the human exon 1 or exon 1′ La mRNA isoform. In all cell lines the respective La mRNAs were translated to La protein. The exon 1 La mRNA-expressing cell lines displayed 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.