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Int. J. Mol. Sci. 2017, 18(7), 1378; doi:10.3390/ijms18071378

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

1
Auckland Cancer Society Research Centre, University of Auckland, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd. Grafton, 1023 Auckland, New Zealand
2
Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd. Grafton, 1023 Auckland, New Zealand
3
Institute of Biotechnology, P.O. Box 56 (Viikinkaari 5), University of Helsinki, FI-00014 Helsinki, Finland
*
Authors to whom correspondence should be addressed.
Received: 27 May 2017 / Revised: 21 June 2017 / Accepted: 22 June 2017 / Published: 27 June 2017
(This article belongs to the Collection Regulation by Non-Coding RNAs)
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Abstract

The long non-coding RNA ANRIL, antisense to the CDKN2B locus, is transcribed from a gene that encompasses multiple disease-associated polymorphisms. Despite the identification of multiple isoforms of ANRIL, expression of certain transcripts has been found to be tissue-specific and the characterisation of ANRIL transcripts remains incomplete. Several functions have been associated with ANRIL. In our judgement, studies on ANRIL functionality are premature pending a more complete appreciation of the profusion of isoforms. We found differential expression of ANRIL exons, which indicates that multiple isoforms exist in melanoma cells. In addition to linear isoforms, we identified circular forms of ANRIL (circANRIL). Further characterisation of circANRIL 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 circANRIL isoforms were almost completely different. Novel exons were also discovered. We also found the family of linear ANRIL 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 circANRIL species, bioinformatic analysis indicated that intronic Arthrobacter luteus (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 “ANRIL” 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 ANRIL in melanoma. View Full-Text
Keywords: melanoma; long noncoding RNA; ANRIL; circular RNA; isoforms; CDKN2A/B melanoma; long noncoding RNA; ANRIL; circular RNA; isoforms; CDKN2A/B
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Sarkar, D.; Oghabian, A.; Bodiyabadu, P.K.; Joseph, W.R.; Leung, E.Y.; Finlay, G.J.; Baguley, B.C.; Askarian-Amiri, M.E. Multiple Isoforms of ANRIL in Melanoma Cells: Structural Complexity Suggests Variations in Processing. Int. J. Mol. Sci. 2017, 18, 1378.

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