2010/01/19

New insights into the regulation of liver de-differentiation, development and human HCC progression.

HuR/Methyl-HuR and AUF1 provide a post-transcriptional regulatory mechanism of MAT1A and MAT2A, the two isoforms of the MAT enzyme, responsible for the levels of hepatic S-adenosylmethionine.

Researchers from the Metabolomics Unit at CICbioGUNE-CIBERehd led by M. Luz Martínez-Chantar and José María Mato have recently published in Gastroenterology a post-transcriptional mechanism that helps to explain the switches between MAT I/III (encoded by the gene MAT1A) and MAT II (encoded by the MAT2A gene). These switches are responsible for the tightly regulated levels of hepatic S-adenosylmethionine, and occur during hepatic processes like de-differentiation, liver development and malignant transformation. The results show that the balance of the mRNA binding proteins AUF1 and methyl-HuR/HuR regulates the stability of the MAT1A and MAT2A mRNA, leading to the changes in the expression of MAT I/III and MAT II. These data strongly support a role for AUF1 and HuR/methyl-HuR in liver de-differentiation, development and human HCC progression through the post-translational regulation of MAT1A and MAT2A mRNAs.