Regulated expression of alternate transcripts from the mouse oncostatin M gene: Implications for interleukin-6 family cytokines

Oncostatin M (OSM) is a member of the IL-6 family of polyfunctional cytokin es, The characterized murine OSM transcript consists of three exons and enc odes a secreted protein. Investigations of mOSM expression using the ribonu clease protection assay demonstrated novel sites of expression in undiffere ntiated but not differentiated pluripotent cells, and revealed the existenc e of alternatively spliced mOSM transcripts. cDNAs representing a novel mOS M transcript (mOSM 13) containing exon 1 spliced directly to exon 3 were is olated from bone marrow using Rapid Amplification of cDNA Ends (RACE) PCR a nd RT-PCR approaches. Expression of the mOSM 13 transcript was regulated in a tissue-specific manner and independently of mOSM transcript production, suggesting that its production is biologically significant. Splicing of exo n 1 directly to exon 3 disrupts the OSM open reading frame of mOSM 13. Init iation of translation at sites within exon 3 of mOSM 13 would yield N-termi nally truncated OSM proteins that are localized within the cell, The omissi on of exon 2 by alternate splicing and the production of intracellular prot eins with alternate biological activities are conserved among several IL-6 family cytokines and are one manifestation of a more general phenomenon; th e production of alternate cytokine transcripts encoding intracellular and e xtracellular proteins. (C) 2000 Academic Press.