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Adeli Lab

ApoB mRNA

Translational Control of ApoB mRNA: RNA-protein interactions involving the 3’UTR and 5’UTR sequences of apoB mRNA

As part of our studies of apoB gene expression and regulation, we have been studying the role of apoB mRNA translation in modulating apoB secretion from hepatocytes. Our laboratory was one of the first groups to present evidence for translational control of apoB mRNA.

In a publication appeared in Biochem. Cell Biol. in 1992 we reported that insulin can attenuate apoB mRNA translation based on direct translation of apoB message in a novel cell free translation system developed from HepG2 cells. Following our initial observations of hormonal regulation of apoB mRNA translation, we have recently focussed our attention to the cis-trans interactions that are responsible for regulation translation.

More specifically, we have been investigating the regulatory elements in the 5’ and 3’ untranslated regions (UTR) of apoB mRNA and how these cis elements may interact with putative trans acting protein factors involved in modulating mRNA translation.

In these studies we have employed heterologous constructs involving apoB UTR sequeneces cloned upstream or downstream of a reporter gene, firefly luciferase. So far we have been able to show that the 5’UTR of apoB mRNA is important in efficient translation of this protein both in vivo and in vitro.

We are currently performing additional studies to identify novel translational protein factors that may interact with the 5’UTR of the apoB message and regulate its translation in the cell. This work has been supported since 1989 by an operating grant from the Natural Sciences and Engineering Research Council of Canada.