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.

Ewelina Szczepanek-Parulska; Witold Szaflarski; Katarzyna Piątek; Bartłomiej Budny; Karolina Jaszczyńska-Nowinka; Maciej Biczysko; Tomasz Wierzbicki; Jerzy Skrobisz; Maciej Zabel; Marek Ruchała

doi:10.18388/abp.2013_2022

Ewelina Szczepanek-Parulska Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland.;
Witold Szaflarski Department of Histology and Embryology, Poznan University of Medical Sciences, Poznań, Poland.;
Katarzyna Piątek Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland; Department of Histology and Embryology, Poznan University of Medical Sciences, Poznań, Poland.;
Bartłomiej Budny Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland.;
Karolina Jaszczyńska-Nowinka Department of Gynecological Oncology, Poznan University of Medical Sciences, Poznań, Poland.;
Maciej Biczysko Department of General, Gastrointestinal and Plastic Surgery, Poznan University of Medical Sciences, Poznań, Poland.;
Tomasz Wierzbicki Department of General, Gastrointestinal and Plastic Surgery, Poznan University of Medical Sciences, Poznań, Poland.;
Jerzy Skrobisz Department of General and Trauma Surgery, with subdivision of Gastroenterological and Endocrine Surgery, District Hospital of Poznań, Poznań, Poland.;
Maciej Zabel Department of Histology and Embryology, Poznan University of Medical Sciences, Poznań, Poland; Department of Histology and Embryology, Wroclaw Medical University, Wrocław, Poland.;
Marek Ruchała Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland.;

DOI: https://doi.org/10.18388/abp.2013_2022

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.