♦ See referenced article, J. Biol. Chem. 2011, 286, 19523–19532
Hyaluronan (HA) is a linear glycosaminoglycan that is ubiquitous in the extracellular matrix. It is involved in a broad range of cellular functions, including the fundamental processes of cell migration and proliferation, and abnormal levels are implicated in an equally broad range of disorders such as tumor malignancy, asthma, wound healing, and organ fibrosis. HA is produced by HA synthases (HAS), and the regulation of HAS genes is crucial for normal cellular function. In this Paper of the Week, Daryn R. Michael and colleagues build on their previous efforts to resolve the mechanism of regulation for HAS2. Prior results suggested that HAS2 mRNA synthesis can be post-transcriptionally regulated by an endogenous antisense RNA, HAS2-AS1. In their current work, the scientists describe the coordinated up-regulation of both HAS2 and HAS2-AS1 transcription in renal proximal tubular epithelial cells in response to interleukin 1β or transforming growth factor β1 and analyze the effects of HAS2-AS1 transcription on HAS2 expression. Their data show that induction of HAS2-AS1 and HAS2 transcription occurs simultaneously and suggest that transcription of the antisense RNA stabilizes or augments HAS2 mRNA expression via formation of an RNA/mRNA heteroduplex.
Cytokine-stimulated up-regulation of HAS2-AS1 and HAS2 expression is coordinated.