Abstract
In recent years, genome-wide analyses of patients have resulted in the identification of a number of neurodevelopmental disorders. Several of them are caused by mutations in genes that encode for RNA-binding proteins. One of these genes is PURA, for which in 2014 mutations have been shown to cause the neurodevelopmental disorder PURA syndrome. Besides intellectual disability (ID), patients develop a variety of symptoms, including hypotonia, metabolic abnormalities as well as epileptic seizures. This review aims to provide a comprehensive assessment of research of the last 30 years on PURA and its recently discovered involvement in neuropathological abnormalities. Being a DNA- and RNA-binding protein, PURA has been implicated in transcriptional control as well as in cytoplasmic RNA localization. Molecular interactions are described and rated according to their validation state as physiological targets. This information will be put into perspective with available structural and biophysical insights on PURA’s molecular functions. Two different knock-out mouse models have been reported with partially contradicting observations. They are compared and put into context with cell biological observations and patient-derived information. In addition to PURA syndrome, the PURA protein has been found in pathological, RNA-containing foci of patients with the RNA-repeat expansion diseases such as fragile X-associated tremor ataxia syndrome (FXTAS) and amyotrophic lateral sclerosis (ALS)/fronto-temporal dementia (FTD) spectrum disorder. We discuss the potential role of PURA in these neurodegenerative disorders and existing evidence that PURA might act as a neuroprotective factor. In summary, this review aims at informing researchers as well as clinicians on our current knowledge of PURA’s molecular and cellular functions as well as its implications in very different neuronal disorders.
Highlights
RNA-binding proteins fulfill a number of important regulatory functions for cell differentiation, cellular asymmetry, and somatic cell activities
It should be taken into account that PURA is ubiquitously expressed in the human body and might fulfill important functions in a range of different tissues (Human Protein Atlas, available from http://www.proteinatlas.org; Uhlen et al, 2015)
It will be necessary to understand which role PURA plays in neural cells
Summary
RNA-binding proteins fulfill a number of important regulatory functions for cell differentiation, cellular asymmetry, and somatic cell activities. Particular attention has been paid to the functions of RNA-binding proteins in neuronal cells where their involvement in messenger RNA (mRNA) transport and translational regulation has been linked to memory. One of them is the so-called Purine-rich single-stranded DNA (ssDNA)-binding protein alpha (PURA, referred to as Pur-alpha), which frequently appears in high-throughput analyses of interaction networks in neuronal tissue. PURA is co-purifying with a multitude of different potential binding partners and has been linked by several of these studies to neural pathologies. Despite a significant body of novel insights from recent studies, still very little is known about its cellular and molecular functions. A critical assessment of our current knowledge is much needed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
