Poly(A)-binding proteins (PABPs) are important regulators of mRNA
translation and stability. In mammals four cytoplasmic PABPs with a similar domain
structure have been described - PABP1, tPABP, PABP4 and ePABP. The vast
majority of research on PABP mechanism, function and sub-cellular localisation is
however limited to PABP1 and little published work has explored the expression of
PABP proteins.
Here, I examine the tissue distribution of PABP1 and PABP4 in mouse and
show that both proteins differ markedly in their expression at both the tissue and
cellular level, contradicting the widespread perception that PABP1 is ubiquitously
expressed. PABP4 is shown to be widely expressed though with an expression
pattern distinct from PABP1, and thus may have a biological function in many
tissues. I have shown that PABP4 associates with polysomes and described
interactions between PABP4 and proteins important for PABP1-mediated
translational activation suggesting that PABP4 plays a similar role in translational
regulation.
Translational inhibition is a common response to cell stress. Following
certain cellular stresses e.g. arsenite, PABP1 localises to cytoplasmic stress granules,
sites of mRNA storage. Here, I show that PABP4 is also a component of stress
granules and have investigated the role of PABPs in stress granule formation. In
contrast, I have shown that both PABP1 and PABP4 relocalise to the nucleus
following UV irradiation in both human and mouse cell lines.
In order to understand the how the UV-induced change in PABP localisation
may be regulated, I have investigated the regulation of PABP nuclear export. I have
found that accumulation of PABP proteins in the nucleus after UV coincides with an
accumulation of poly(A)+ RNA, indicative of a block in mRNA export, an effect
which has not been previously characterized. My working model is that nuclear
export of PABPs may be dependent on mRNA export, inhibition of which leads to
nuclear accumulation of PABPs after UV, which may in turn augment translational
inhibition
