c-myc RNA degradation in growing and differentiating cells: possible alternate pathways.
Transcripts of the proto-oncogene c-myc are composed of a rapidly degraded polyadenylated RNA species and an apparently much more stable, nonadenylated RNA species. In this report, the extended kinetics of c-myc RNA turnover have been examined in rapidly growing cells and in cells induced to differentiate. When transcription was blocked with actinomycin D in rapidly growing cells, poly(A)+ c-myc was rapidly degraded (t1/2 = 12 min). c-myc RNA lacking poly(A) initially remained at or near control levels; however, after 80 to 90 min it was degraded with kinetics similar to those of poly(A)+ c-myc RNA. These bizarre kinetics are due to the deadenylation of poly(A)+ c-myc RNA to form poly(A)- c-myc, thereby initially maintaining the poly(A)- c-myc RNA pool when transcription is blocked. In contrast to growing cells, cells induced to differentiate degraded both poly(A)+ and poly(A)- c-myc RNA rapidly. The rapid disappearance of both RNA species in differentiating cells suggests that a large proportion of the poly(A)+ c-myc RNA was directly degraded without first being converted to poly(A)- c-myc RNA. Others have shown that transcriptional elongation of the c-myc gene is rapidly blocked in differentiating cells. We therefore hypothesize that in differentiating cells a direct, rapid degradation of poly(A)+ c-myc RNA may act as a backup or fail-safe system to ensure that c-myc protein is not synthesized. This tandem system of c-myc turnoff may also make cells more refractory to mutations which activate constitutive c-myc expression.
Swartwout
S G
SG
Department of Human Genetics, Roswell Park Memorial Institute, Buffalo, New York 14263.
Kinniburgh
A J
AJ
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D011061:Poly A / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012322:RNA Precursors; D011061:Poly A