Isolation of cDNA clones encoding small nuclear ribonucleoparticle-associated proteins with different tissue specificities.

Alternative RNA processing, such as brain- and heart-specific generation of calcitonin gene-related peptide (CGRP) transcripts from the calcitonin/CGRP gene, is thought to be mediated by tissue-specific factors. We have cloned three related but distinct cDNAs encoding small nuclear ribonucleoparticle (snRNP)-associated proteins from rat PC12 cells. One clone (Sm51) has the capacity to encode a 240-amino acid protein and its RNA transcript is expressed selectively in rat brain and pituitary but not in heart. A related cDNA, designated Sm11, predicts a protein highly homologous to but distinct from Sm51. The Sm11 transcript is very abundant in heart but barely detectable in brain. Sm51 and Sm11 appear to encode the brain and heart forms of a 28-kDa snRNP-associated protein detected by anti-Sm serum, respectively. A third clone (Sm21) encodes a protein with an altered N terminus relative to Sm51. The Sm51 transcript is expressed in the pituitary, and analysis of the pituitaries of transgenic mice harboring a mouse metallothionein I promoter-calcitonin/CGRP fusion gene reveals the splice choice to be predominantly CGRP. In situ hybridization indicates Sm51 RNA is expressed throughout neuronal structures within rat brain, including the inferior colliculus, which does not possess the machinery to generate CGRP. Although Sm51 alone cannot be sufficient to account for CGRP splicing choice in all tissues, the demonstration of discrete tissue-specific expression patterns of closely related snRNP-associated proteins is consistent with their potential role in differential RNA processing events.