Regulation of RAGE splicing by hnRNP A1 and Tra2β-1 and its potential role in AD pathogenesis.

2015: FChai; XHChen; SCCui; FHDing; HLLi; YXLi; XYLiu; JBSu; FYSun; ZYWu; PXu; JJZhao;

J Neurochem.2015;133(2):187-98.10.1111/jnc.13069.

NLM PMID: 25689357

Article abstract

The receptor for advanced glycation end products (RAGE) gene expresses two major alternative splicing isoforms, full-length membrane-bound RAGE (mRAGE) and secretory RAGE (esRAGE). Both isoforms play important roles in Alzheimer's disease (AD) pathogenesis, either via interaction of mRAGE with β-amyloid peptide (Aβ) or inhibition of the mRAGE-activated signaling pathway. In the present study, we showed that heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and Transformer2β-1 (Tra2β-1) were involved in the alternative splicing of mRAGE and esRAGE. Functionally, two factors had an antagonistic effect on the regulation. Glucose deprivation induced an increased ratio of mRAGE/esRAGE via up-regulation of hnRNP A1 and down-regulation of Tra2β-1. Moreover, the ratios of mRAGE/esRAGE and hnRNP A1/Tra2β-1 were increased in peripheral blood mononuclear cells from AD patients. The results provide a molecular basis for altered splicing of mRAGE and esRAGE in AD pathogenesis. The receptor for advanced glycation end products (RAGE) gene expresses two major alternative splicing isoforms, membrane-bound RAGE (mRAGE) and secretory RAGE (esRAGE). Both isoforms play important roles in Alzheimer's disease (AD) pathogenesis. Mechanism for imbalanced expression of these two isoforms in AD brain remains elusive. We proposed here a hypothetic model to illustrate that impaired glucose metabolism in AD brain may increase the expression of splicing protein hnRNP A1 and reduce Tra2β-1, which cause the imbalanced expression of mRAGE and esRAGE.

Research Topics
• Diseases
   Alzheimer Disease
   Neuroblastoma

Title and Abstract from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Data mined from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Last MEDLINE®/PubMed® update: 1st of December 2015