Abstract

Growing evidences suggest the involvement of the endoplasmic reticulum (ER) stress in lipid metabolism and in the development of some liver disease such as steatosis. The transcription factor SREBP-1 modulates the expression of several enzymes involved in lipid synthesis. Previously, we showed that ER stress increased the SREBP-1a protein level in Hep G2 cells, by inducing a cap-independent translation of SREBP-1a mRNA, through an internal ribosome entry site (IRES), located in its leader region. Here, we report evidence that the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) interacts with 5’-UTR of SREBP-1a mRNA, as an IRES trans-acting factor (ITAF), regulating SREBP-1a expression in Hep G2 cells and in primary rat hepatocytes. Overexpression of hnRNP A1 in Hep G2 cells and in rat hepatocytes increased both the SREBP-1a IRES activity and SREBP-1a protein level. Knockdown of hnRNP A1 by small interfering RNA reduced either the SREBP-1a IRES activity and SREBP-1a protein level. HnRNP A1 mediates the increase of SREBP-1a protein level and SREBP-1a IRES activity in Hep G2 cells and in rat hepatocytes upon tunicamycin- and thapsigargin-induced ER stress. The induced ER stress triggered the cytosolic relocation of hnRNP A1 and caused the increment of hnRNP A1 bound to the SREBP-1a 5’-UTR. These data indicate that hnRNP A1 participates in the IRES-dependent translation of SREBP-1a mRNA through RNA-protein interaction. Different content of hnRNP A1 was found in nuclei from liver of high fat diet-fed mice versus standard diet fed-mice, suggesting an involvement of ER stress-mediated hnRNP A1 subcellular redistribution on the onset of metabolic disorders.

Autore Pugliese

• Siculella Luisa , Damiano Fabrizio

Tutti gli autori

• Damiano F. , Rochira A. , Tocci R. , Alemanno S , Gnoni A. , Siculella L.

Titolo volume/Rivista

BIOCHEMICAL JOURNAL

Anno di pubblicazione

2013

ISSN

0264-6021

ISBN

Non Disponibile

Numero di citazioni Wos

22

Ultimo Aggiornamento Citazioni

28/04/2018

Numero di citazioni Scopus

24

Ultimo Aggiornamento Citazioni

28/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile