Characterisation of novel splicing variants of the tyrosine hydroxylase C-terminal domain in human neuroblastic tumours

Josep Roma, Ester Saus, Marc Cuadros, Jaume Reventós, Josep Sánchez De Toledo, Soledad Gallego*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

Alternative splicing of human tyrosine hydroxylase (hTH) transcripts appears to occur mainly in the N-terminal domain, giving rise to at least eight different isoforms. We recently reported the existence of hTH transcript variants resulting from splicing of exons 8 and 9, within a region previously thought to be constant. The mRNA distribution of these novel hTH isoforms in neuroblastic tumours and in foetal adrenal glands was analysed by conventional and real-time RT-PCR. The presence of the target protein was determined by Western blotting, immunoprecipitation and protein analysis. Transcripts lacking exons 8 and 9 were widely distributed in the tissues analysed. Characterisation of full-length mRNA revealed that splicing of exons 8 and 9 was always associated with splicing of exons 2 (hTH-Δ2,8,9) or 1b and 2 (hTH-Δ1b,2,8,9). In addition, one variant detected on Western blots in several tumours fits the predicted size (58 kDa) of the isoforms lacking exons 8 and 9. In conclusion, the two novel isoforms reported here (hTH-Δ2,8,9 and hTH-Δ1b,2,8,9) represent the first full-length isoforms with alternative splicing in the hTH C-terminal domain. These results demonstrate for the first time the existence of hTH isoforms Δ2,8,9 and Δ1b,2,8,9. Their general distribution in neuroblastoma and adrenal glands and translation into protein suggest a significant functional role for these novel hTH isoforms, which merit further study.

Original languageAmerican English
Pages (from-to)419-426
Number of pages8
JournalBiological Chemistry
Volume388
Issue number4
DOIs
Publication statusPublished - 1 Apr 2007

Keywords

  • Adrenal medulla
  • Alternative splicing
  • Neuroblastoma
  • Tyrosine hydroxylase isoforms

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