Multiple Isoforms of ANRIL in Melanoma Cells: Structural Complexity Suggests Variations in Processing

The long non-coding RNA , antisense to the locus, is transcribed from a gene that encompasses multiple disease-associated polymorphisms. Despite the identification of multiple isoforms of , expression of certain transcripts has been found to be tissue-specific and the characterisation of transcripts remains incomplete. Several functions have been associated with In our judgement, studies on functionality are premature pending a more complete appreciation of the profusion of isoforms. We found differential expression of exons, which indicates that multiple isoforms exist in melanoma cells. In addition to linear isoforms, we identified circular forms of (). Further characterisation of in two patient-derived metastatic melanoma cell lines (NZM7 and NZM37) revealed the existence of a rich assortment of circular isoforms. Moreover, in the two melanoma cell lines investigated, the complements of isoforms were almost completely different. Novel exons were also discovered. We also found the family of linear was enriched in the nucleus, whilst the circular isoforms were enriched in the cytoplasm and they differed markedly in stability. With respect to the variable processing of species, bioinformatic analysis indicated that intronic (Alu) restriction endonuclease inverted repeats and exon skipping were not involved in selection of back-spliced exon junctions. Based on our findings, we hypothesise that "" has wholly distinct dual sets of functions in melanoma. This reveals the dynamic nature of the locus and constitutes a basis for investigating the functions of in melanoma.