Cysteine/tyrosine-rich 1 (CYYR1) is a gene we previously identified on human chromosome 21 (Hsa21). CYYR1 was initially characterized as a four-exon gene that predicts a 154-amino acid product. We provide the first detailed description of the human CYYR1 locus. It is composed of a multigene system, which includes at least seven CYYR1 alternative spliced isoforms and a new CYYR1 antisense gene. In particular, we cloned the following isoforms: CYYR1-1,2,3,4b and CYYR1-1,2,3b present a different 3´ transcripted region; CYYR1-1,2,4 lacks exon 3; CYYR1-1,2,2bis,3,4 presents an additional exon between exon 2 and exon 3; CYYR1-1b,2,3,4 presents a different 5´ untranslated region when compared to CYYR1. The meaningful differences in the protein isoforms of CYYR1 locus could indicate different functions and localizations of the predicted proteins. Moreover, we cloned a long transcript overlapping with CYYR1 as an antisense RNA, probably a non-coding RNA. In order to verify the Hsa21 locus expression profile in altered conditions such as cancer and aneuploidy, expression analysis was performed in different tumour cell lines and in trisomy 21 (CCL54) and euploid fibroblasts (CCL110). The results obtained indicate a bare expression of the multi-transcript CYYR1 in all the tumour cell lines studied, with the exception of U2OS, as well as in CCL110, while it is clearly detectable in CCL54. The characterization of the CYYR1 locus is a first step to clarify a possible role of the human locus related to tumorigenesis and Down syndrome disease. For this purpose, U2OS and CCL could be cell model systems useful to verify the real expression of the predicted proteins by studying the differences in the localization and/or the functional interaction and competition between each CYYR1 isoform. The results of the present study highlight the necessity to analyse thoroughly human gene loci that are still orphaned of role comprehension, but that could be related to complex diseases.

Characterization of human gene locus CYYR1: a complex multi-transcript system.

PELLERI, MARIA CHIARA;CASADEI, RAFFAELLA;VITALE, LORENZA;FACCHIN, FEDERICA;CANAIDER, SILVIA;STRIPPOLI, PIERLUIGI;PIOVESAN, ALLISON;BIANCONI, EVA;FRABETTI, FLAVIA
2013

Abstract

Cysteine/tyrosine-rich 1 (CYYR1) is a gene we previously identified on human chromosome 21 (Hsa21). CYYR1 was initially characterized as a four-exon gene that predicts a 154-amino acid product. We provide the first detailed description of the human CYYR1 locus. It is composed of a multigene system, which includes at least seven CYYR1 alternative spliced isoforms and a new CYYR1 antisense gene. In particular, we cloned the following isoforms: CYYR1-1,2,3,4b and CYYR1-1,2,3b present a different 3´ transcripted region; CYYR1-1,2,4 lacks exon 3; CYYR1-1,2,2bis,3,4 presents an additional exon between exon 2 and exon 3; CYYR1-1b,2,3,4 presents a different 5´ untranslated region when compared to CYYR1. The meaningful differences in the protein isoforms of CYYR1 locus could indicate different functions and localizations of the predicted proteins. Moreover, we cloned a long transcript overlapping with CYYR1 as an antisense RNA, probably a non-coding RNA. In order to verify the Hsa21 locus expression profile in altered conditions such as cancer and aneuploidy, expression analysis was performed in different tumour cell lines and in trisomy 21 (CCL54) and euploid fibroblasts (CCL110). The results obtained indicate a bare expression of the multi-transcript CYYR1 in all the tumour cell lines studied, with the exception of U2OS, as well as in CCL110, while it is clearly detectable in CCL54. The characterization of the CYYR1 locus is a first step to clarify a possible role of the human locus related to tumorigenesis and Down syndrome disease. For this purpose, U2OS and CCL could be cell model systems useful to verify the real expression of the predicted proteins by studying the differences in the localization and/or the functional interaction and competition between each CYYR1 isoform. The results of the present study highlight the necessity to analyse thoroughly human gene loci that are still orphaned of role comprehension, but that could be related to complex diseases.
XV A.I.B.G., Arcavacata di Rende (CS), 27-28 settembre 2013, Programma & Abstracts
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M.C. Pelleri; R. Casadei; L. Vitale; F. Facchin; S. Canaider; P. Strippoli; M. Vian; A. Piovesan; E. Bianconi; F. Piva; F. Frabetti.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/399112
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