Use of a retrotranscription-activated marker ( RAM ) to select for targetron integrations. A targetron with a RAM cassette is expressed from a donor plasmid. The RAM cassette consists of a selectable marker gene, such as an antibiotic-resistance gene (kanR), inserted within the intron DIV in the antisense orientation, but interrupted by an efficiently self-splicing group I intron (the phage T4 td intron) in the sense orientation, thereby preventing expression of the kanR marker gene from the donor plasmid. Transcription of the targetron carrying the RAM from the donor plasmid yields a primary transcript from which the group I intron is spliced to reconstitute the kanR marker and the group II intron is spliced to yield RNPs that retrohome into a DNA target site. After retrohoming, the reconstituted kanR marker is expressed from its own promoter, enabling selection for targetron integrations.