The Human Long Noncoding RNA Wilms Tumour 1 Antisense Locus, from an Evolutionary Perspective to Functional Insights

Abstract

The Wilms’ tumor suppressor gene 1 (WT1) encodes a structurally diverse and multifunctional protein with tightly controlled expression throughout the development of several organ systems, particularly essential for genitourinary development, sex determination, as well as nephrogenesis. How WT1 locus contributes to the shift from normal function nor developmental disease is not well understood. Bidirectional sense and antisense transcription are abundant across vertebrates suggesting that antisense transcripts may be relevant, but their biological function is largely unknown. However, the analysis of a novel knock-out mouse demonstrated that an ultra-conserved WT1 transcript RNA (UCWT2) stabilizes Awt1 RNA expression and displays phenotypic changes, resulting in changes at embryonic survival, as well as liquid homeostasis. We demonstrate that WT1 antisense transcript evolutionary parallels vertebrate morphological urinary systems and may act as regulator in WT1 locus, implying a physiological effect, from in silico to in vitro tools.