Alternative 3' acceptor site in the exon 2 of human PAX8 gene resulting in the expression of unknown mRNA variant found in thyroid hemiagenesis and some types of cancers

Acta Biochim Pol. 2013;60(4):573-8. Epub 2013 Dec 16.

Abstract

PAX8 gene encodes one of the transcription factors engaged in the regulation of proper development of thyroid gland as well as Müllerian and renal/upper urinary tracts. So far, six alternatively spliced transcripts were reported, however, sequences of only four were deposited in the NCBI database. Here, we evaluate a fragment of a novel variant of PAX8 mRNA formed by an alternative 3' acceptor site located in the second exon. The molecular outcome encompasses extension of the 5' untranslated region of exon two by 97 nucleotides as is evident from mRNA. This new insert may impair binding of mRNA to the ribosome and in consequence significantly decrease expression of the PAX8 protein. Here, we show for the first time that the novel insert in exon two might be associated with congenital thyroid hemiagenesis and influence development of different types of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • 5' Untranslated Regions
  • Alternative Splicing / genetics
  • Amino Acid Sequence
  • Exons
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors / genetics*
  • Paired Box Transcription Factors / metabolism
  • RNA Splice Sites / genetics*
  • RNA, Messenger / genetics
  • Thyroid Gland / metabolism*
  • Thyroid Gland / pathology

Substances

  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • Paired Box Transcription Factors
  • RNA Splice Sites
  • RNA, Messenger