Sequence determinants of c-myc mRNA turn-over: influence of 3' and 5' non-coding regions

Abstract

Normal c-myc RNAs are very unstable with a half-life of less than 30 min whereas those rearranged in 5', as found in Burkitt's lymphomas and mouse plasmacytomas, are significantly more stable. To learn about the sequence determinants controlling their turnover, we have studied naturally occurring and artificially constructed c-myc RNAs rearranged in 5' or 3'. The first conclusion is that sequences necessary for rapid c-myc RNAs turnover are localized in their 3' untranslated region. The second conclusion is that stabilization of truncated c-myc RNAs in tumors does not result from deletion of the non-coding first exon but rather from its replacement by intronic and/or exogenous sequences. This latter conclusion rests on two lines of evidence: (i) deleting the 5' rearranged sequences from the relatively stable MOPC 315 RNA restores its complete instability (pSV c-myc 1); (ii) reciprocally, appending intron 1 sequences 5' to otherwise unstable germline c-myc exons 2 and 3 have a dramatic stabilizing effect (pIM 0).