Rapid c-myc mRNA degradation does not require (A + U)-rich sequences or complete translation of the mRNA.

Abstract

The c-myc proto-oncogene encodes a highly unstable mRNA. Stabilized, truncated myc transcripts have been found in several human and murine tumors of hematopoietic origin. Recently, two tumors expressing 3' truncated c-myc mRNAs that were five times more stable than normal myc transcripts, were described. We have tried to determine the cause of the increased stability of the 3' truncated myc transcripts by studying the half-life of mutated c-myc mRNAs. The c-myc 3' untranslated region has been shown to contain sequences that confer mRNA instability. Possible candidates for such sequences are two (A + U)-rich regions in the 3' end of the c-myc RNA that resemble RNA destabilizing elements present in the c-fos and GMCSF mRNAs. We show that deletions in the (A + U)-rich regions do not stabilize c-myc messengers, and that hybrid mRNAs containing SV40 sequences at their 3' ends and terminating at an SV40 polyadenylation signal decay as quickly as normal c-myc transcripts. Our results indicate that neither the loss of (A + U)-rich sequences nor the mere addition of non-myc sequences to the 3' end of the mRNA lead to stabilization. We also show that rapid degradation of c-myc mRNA does not require complete translation of the coding sequences.