Background RNA-binding proteins (RBPs) are fundamental regulators of cellular biology that affect all steps in the generation and processing of RNA molecules. Recent evidence suggests that regulation of RBPs that modulate both RNA stability and translation may have a profound effect on the proteome. However, regulation of RBPs in clinically relevant experimental conditions has not been studied systematically. Methods We used RNA interactome capture, a method for the global identification of RBPs to characterize the global RNA-binding proteome (RBPome) associated with polyA-tailed RNA species in murine ciliated epithelial cells of the inner medullary collecting duct. To study regulation of RBPs in a clinically relevant condition, we analyzed hypoxia-associated changes of the RBPome. Results We identified .1000 RBPs that had been previously found using other systems. In addition, we found a number of novel RBPs not identified by previous screens using mouse or human cells, suggesting that these proteins may be specific RBPs in differentiated kidney epithelial cells. We also found quantitative differences in RBP-binding to mRNA that were associated with hypoxia versus normoxia. Conclusions These findings demonstrate the regulation of RBPs through environmental stimuli and provide insight into the biology of hypoxia-response signaling in epithelial cells in the kidney. A repository of the RBPome and proteome in kidney tubular epithelial cells, derived from our findings, is freely accessible online, and may contribute to a better understanding of the role of RNA-protein interactions in kidney tubular epithelial cells, including the response of these cells to hypoxia.
Introduction: Aβ-related angiitis (ABRA) is a very rare disease entity with combined features of cerebral amyloid angiopathy and primary angiitis of the CNS. However, the pathogenesis has not been conclusively described yet. Interestingly though, a possible paraneoplastic origin has been reported in the past. ABRA leads to severe encephalopathy with a broad spectrum of unspecific neurological symptoms and usually occurs in older patients. Because of the response to immunological treatment, it is important to confirm the diagnosis as fast as possible. Unfortunately, the pathway to a definite diagnosis is often complicated and prolonged. Case Report: Here, we describe a 48-year-old-female patient presenting headache, behavioral changes as well as subacute fatigue and epileptic seizures in the recent past. The initial neuroradiological examination demonstrated extended lesions in the left hemisphere compatible with an inflammatory or neoplastic disease. After extensive investigations, initially without a definite result, we finally validated the diagnosis of ABRA by brain biopsy. Shortly afterwards a routine check-up revealed an invasive mammary carcinoma. Owing to a mandatory mastectomy and chemotherapy, an immunosuppressive therapy was not implemented. Conclusions: The reported case demonstrates our diagnostic approach and the clinical difficulties in validating a rare cause of encephalopathy in a young patient with nonspecific clinical and neuroradiological findings. Because of the possibility of an effective treatment, it is important to consider ABRA in the differential diagnosis especially when blood tests, analysis of cerebrospinal fluid, and angiography show normal results. Since a paraneoplastic genesis is presumed, a search for an underlying tumor disease should be considered.
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