A 3' truncation of MYC caused by chromosomal translocation in a human T-cell leukemia increases mRNA stability.
The proto-oncogene MYC is rearranged at its 3' end in the human T-cell leukemia line Hut 78 as a result of a translocation between the long arms of chromosomes 8 and 2. The nucleotide sequence at the breakpoint shows that the rearranged allele of MYC is truncated 24 nucleotides before the first poly(A)-addition signal. The 3' truncated MYC lacks a 61 nucleotide AT-rich sequence that has been reported to mediate selective mRNA degradation. We show that the truncation results in prolonged stability of MYC mRNA: the half life of the MYC mRNA in Hut 78, as well as in Rat 1A cells transfected with the truncated allele of MYC is increased by at least 5-fold. Our results document yet another mechanism by which MYC may be rendered pathogenic and dramatize the importance of mRNA stability in the regulation of MYC activity.
Aghib
D F
DF
Dipartimento di Genetica e di Biologia dei Microorganisimi, Università di Milano, Italy.
Bishop
J M
JM
Ottolenghi
S
S
Guerrasio
A
A
Serra
A
A
Saglio
G
G
D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004355:Drug Stability; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000235:genetics*; D014178:Translocation, Genetic
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger