Transcriptional-translational regulation of muscle-specific protein synthesis and its relationship to chondrogenic stimuli.
Demineralized bone (bone matrix) has a well-characterized ability to evoke the re-differentiation of cells derived from skeletal muscle into chondrocytes. Recent investigations in this laboratory have shown that muscle-specific (alpha) actin synthesis continues throughout redifferentiation. Conversely, expression of the cartilage phenotype is associated with repression of muscle-specific enzyme synthesis. The present experiments were undertaken to determine the mode of genomic regulation responsible for control of these muscle-specific syntheses. As part of these experiments, we investigated the ability of embryonic and adult RNA to direct translation in vitro. The results indicate that unfractionated (total) RNA is capable of directing the efficient synthesis of actin, but not myosin heavy or light chains. Decreased abundance of polyadenylated mRNA cannot account for lack of myosin synthesis. Polyadenylated mRNA, however, directed synthesis of actin and myosin with an efficiency greater than that of total RNA. This data suggested that embryonic total RNA was subject to translational control. Dot blot hybridization against cDNA probes for alpha-actin, myosin heavy chain, and fast light chains demonstrated that myogenic cells were subject to a pattern of mixed transcriptional and translational control. It is hypothesized that full expression of the muscle phenotype involves sequential release of transcriptional, and subsequently, the translational controls. We have also observed that cultures of skeletal muscle on bone matrix contain mRNA for muscle-specific proteins, even through the period normally characterized by chondrogenesis. In the absence of concurrent enzyme protein synthesis, it appears that one action of bone matrix is to continue genomic controls that in the source skeletal muscle maintain the genome in an embryonic (translationally repressed) state.
Nathanson
M A
MA
Bush
E W
EW
Vanderburg
C
C
D000818:Animals; D001483:Base Sequence; D002356:Cartilage / Q000166:cytology*; D003470:Culture Media; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D008970:Molecular Weight; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D009693:Nucleic Acid Hybridization; D011061:Poly A / Q000378:metabolism; D011247:Pregnancy; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic
D003470:Culture Media; D009124:Muscle Proteins; D012333:RNA, Messenger; D011061:Poly A