title: Alterations in polyadenylation and its implications for endocrine disease.
abstract: BACKGROUND
  Polyadenylation is the process in which the pre-mRNA is cleaved at the poly(A) site and a poly(A) tail is added - a process necessary for normal mRNA formation. Genes with multiple poly(A) sites can undergo alternative polyadenylation (APA), producing distinct mRNA isoforms with different 3' untranslated regions (3' UTRs) and in some cases different coding regions. Two thirds of all human genes undergo APA. The efficiency of the polyadenylation process regulates gene expression and APA plays an important part in post-transcriptional regulation, as the 3' UTR contains various cis-elements associated with post-transcriptional regulation, such as target sites for micro-RNAs and RNA-binding proteins. Implications of alterations in polyadenylation for endocrine disease: Alterations in polyadenylation have been found to be causative of neonatal diabetes and IPEX (immune dysfunction, polyendocrinopathy, enteropathy, X-linked) and to be associated with type I and II diabetes, pre-eclampsia, fragile X-associated premature ovarian insufficiency, ectopic Cushing syndrome, and many cancer diseases, including several types of endocrine tumor diseases.
  
  
  CONCLUSIONS
  Recent developments in high-throughput sequencing have made it possible to characterize polyadenylation genome-wide. Antisense elements inhibiting or enhancing specific poly(A) site usage can induce desired alterations in polyadenylation, and thus hold the promise of new therapeutic approaches.
  
  
  CONCLUSIONS
  This review gives a detailed description of alterations in polyadenylation in endocrine disease, an overview of the current literature on polyadenylation and summarizes the clinical implications of the current state of research in this field.
authors: Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Copenhagen, Denmark.
authors: Anders
authors: A
authors: Rehfeld
authors: Mireya
authors: M
authors: Plass
authors: Anders
authors: A
authors: Krogh
authors: Lennart
authors: L
authors: Friis-Hansen
keywords: IGF-1; RET; antisense elements; diabetes; gene expression regulation; polyadenylation; pre-eclampsia
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