ISOLATION AND CHARACTERIZATION OF A CDNA CLONE ENCODING FOR RAT CSF-1GENE - POSTTRANSCRIPTIONAL REPRESSION OCCURS IN MYOGENIC DIFFERENTIATION

A major CSF-1 (Colony-Stimulating Factor 1) mRNA 4.0 kb long was expre ssed during the proliferation of the L6alpha1 rat myogenic cells and w as down-regulated after their differentiation into myotubes. A complet e cDNA encoding the rat CSF-1 gene (rmCSF-1) was isolated from a cDNA library of L6alpha1 myoblasts and sequenced. The overall deduced amino acid sequence was 100% and 68% identical to the mouse and human CSF-1 , respectively. While the previously reported mechanisms about the reg ulation of CSF-1 expression in TPA-treated-monocytes (Horiguchi, J., S ariban, E. and Kufe, D. (1988) Mol. Cell. Biol. 8, 3951-3954) and in f ibroblasts (Falkenburg, J.H.F., Harrington, M.A., De Paus, R.A., Walsh , M.K., Daub, R., Landegent, J.E. and Broxmeyer, H.E. (1991) Blood 78, 658-665) involved a control at the transcriptional level, in contrast , the CSF-1 mRNA (half-life approximately 3 h in L6alpha1 myoblasts) w as post-transcriptionally down-regulated during myogenesis. Inhibition of protein synthesis with cycloheximide (CHX) increased differentiall y the half-life of CSF-1 mRNA in L6alpha1 myotubes compared to L6alpha 1 myoblasts. Finally, L6alpha1 myoblasts were shown to synthesize a 14 0 kDa homodimeric form of CSF-1. Thus, these findings, together with o ther results, indicate that CSF-1 gene products may play a role in the normal and neoplastic proliferation of muscular cells.