ESPE Yearbook of Paediatric Endocrinology

Brief Summary:This basic research study examined post-transcriptional regulation of the human androgen receptor (AR) using three different human cell lines. The authors studied the structure of two key AR isoforms, full length (AR-FL) and truncated (AR-V7), by computational and experimental analyses and revealed novel insights into the functionally relevant structures in the 5′ and 3′ UTRs of AR-FL for AR expression.

The AR plays important roles for numerous human disorders including androgen insensitivity syndrome (AIS) and various cancers, e.g. prostate cancer. AR has been well studied at the genetic and protein level, but there is still much to be learned about its regulation at the mRNA level to fill gaps in knowledge and find novel targets for treatment of related disease. Therefore, basic studies are essential. Post-transcriptional regulation of mRNA can be controlled by RNA secondary structure, which may affect splicing, translation, degradation, and localization. These regulatory structures are predominantly localized in the 5′ and 3′ untranslated regions (UTRs) of genes, as studied by Rouse et al for the AR. They can provide access for regulators such as RNA binding proteins and microRNAs.

Understanding the complex (post-transcriptional) regulation of the AR is vital in understanding and treating of related diseases as we still don’t know the patho-aetiology of many of these.

Related article showing novel regulatory mechanisms of AR expression involved in AIS:

Formin-mediated nuclear actin at androgen receptors promotes transcription.

Reference: 1. Julian Knerr, Ralf Werner, Carsten Schwan, Hong Wang, Peter Gebhardt, Helga Grötsch, Almuth Caliebe, Malte Spielmann, Paul-Martin Holterhus, Robert Grosse, Nadine C. Hornig. Nature 617, 616–622 (2023). doi: 10.1038/s41586-023-05981-1.