Cl. Jopling et Ae. Willis, N-myc translation is initiated via an internal ribosome entry segment thatdisplays enhanced activity in neuronal cells, ONCOGENE, 20(21), 2001, pp. 2664-2670
Eukaryotic translation can be initiated either by a cap-dependent mechanism
or by internal ribosome entry, a process by which ribosomes are directly r
ecruited to structured regions of mRNA upstream of the initiation codon, We
analysed the 5' untranslated region (UTR) of the proto-oncogene N-myc, and
demonstrated by transfections in a dicistronic vector system that it conta
ins a potent internal ribosome entry segment (IRES), The IRES is similar in
length to the c-myc [RES and the activities of these IRESs are comparable
in non-neuronal cells. Transfections were also carried out in cell lines de
rived from neuroblastomas, in which N-myc is expressed, and in a neuronal p
recursor cell line. In these cells the N-myc IRES is up to seven times more
active than that of c-myc, suggesting that neuronal-specific non-canonical
trans-acting factors are used by the N-myc but not the c-myc IRES, N-myc e
xpression is increased by gene amplification in many neuroblastomas, but th
is is the first example of a translational mechanism by which N-myc express
ion could be further increased. The discovery of an IRES that displays enha
nced activity in neuronal cell lines has important potential as a tool for
protein expression in neural tissue.