Alternate mRNA processing of the hepatocyte nuclear factor genes and its role in monogenic diabetes

Abstract

Variation in mRNA processing has the capacity to exert fine control over gene expression in most cell types. The hepatic nuclear factor genes, like approximately 74% of the genome, produce multiple transcripts. Hepatic nuclear factor isoforms exhibit both spatial and temporal variation in expression. In this review, the known isoforms of the hepatocyte nuclear factor-1α, hepatocyte nuclear factor-1β and hepatocyte nuclear factor-4α genes are described and their properties are compared. Finally, data are discussed regarding the influence of hepatocyte nuclear factor-1α alternate mRNA processing on the clinical phenotype of maturity-onset diabetes of the young.

Keywords::

• genotype–phenotype relationship
• HNF1A
• HNF1B
• HNF4A
• maturity-onset diabetes of the young
• mRNA processing
• spatial regulation
• temporal regulation

Acknowledgements

I would like to acknowledge my colleagues Professor Andrew Hattersley, Professor Sian Ellard, Emma Edghill, Dr Jayne Minton and Sarah Flanagan for helpful discussion and critical comments on this manuscript. I am also grateful to the Peninsula Medical School (Exeter, UK) for supporting my research and the RCUK and Diabetes UK for funding my studies.