Organization of TERC-ITS loci. RNA sequences are in italic. The RNA sequences involved in the events and the DNA sequences corresponding to them (that is, complementary to retrotranscribed sequences) are in light colors (orange, grey and light blue) while the DNA sequences derived from retrotranscription of the RNA are in dark colors (red, black and dark blue). (a) Sequence of the mouse telomerase RNA component. The nucleotides of the canonical telomerase template, located near the 5' end, are shown in orange (nucleotides 3-10). Nucleotides adjacent to the template that are retrotranscribed together with the first inserted hexamer are grey underlined. The nucleotides of the 3' domain of TERC involved in the TERC-ITS loci are indicated in light blue. The 17 nt core sequence, present in all TERC-ITSs, has a blue background. In the 3' domain of the RNA, the mouse TERC sequence homologous to the human TERC sequence interacting with Ku is underlined. (b) Example of a mouse specific TERC-ITS locus (MMU9qA5). The top row shows the 5' domain of TERC containing the canonical template (orange) and the adjacent sequence (grey underlined). The second row shows the sequence of the mouse locus: telomeric repeats are in red; the nucleotides complementary to those adjacent to the hexameric template are black underlined; the light blue nucleotides indicate the region derived from the 3' domain of TERC. The third row reports, in light blue, the sequence of the 3' domain of TERC from nucleotides 314 to nucleotides 373. The bottom row shows the sequence of the orthologous empty rat locus RNO8q23. The CG dinucleotide (yellow) is present both in the ancestral rat sequence, at the 3' end of the break, and in the region of the TERC RNA immediately preceding the retrotranscribed 3' domain. (c) Overall organization of TERC-ITS loci. At the top is the structure of TERC: orange oval, canonical template; grey square, adjacent nucleotides; light blue strip, 3' domain. At the bottom is the organization of the double-stranded DNA at TERC-ITS loci: light blue strip, sequence corresponding to the 3' domain of TERC; blue strip, complementary sequence; black square, sequence complementary to the nucleotides adjacent to the canonical template; grey square, sequence corresponding to the nucleotides adjacent to the canonical template; red ovals, TTAGGG repeats; orange ovals, complementary repeats.