|dc.description.abstract||The poly(A)-binding proteins (PABPs) are a family of eukaryotic RNA-binding
proteins with key roles in mRNA translation and stability. The molecular function of
PABPs have been largely revealed through study of the prototypical cytoplasmic
poly(A)-binding protein, PABP1. Thus, little is known regarding other PABP family
members. PABP5 contains four RNA-recognition motifs characteristic of the
cytoplasmic PABPs yet is structurally distinct as it lacks a portion of the C-terminus.
This region contains a proline-rich section linked to a globular domain that facilitates
a number of protein-protein interactions. To date, little information has been
presented regarding the expression of PABP5 and there is no data pertaining to the
function of this protein, despite being mapped to a region of the X-chromosome
associated with human pathological conditions.
In this thesis, I present the first data documenting the expression of PABP5 within
mouse tissues, and find it to be expressed at the highest levels within the brain,
ovary, and testis. The limited data available suggests that gonads may be the only
tissue to contain all PABPs therefore I additionally describe the expression of
PABP1 and PABP4 to ascertain their cellular distribution within these tissues. This
revealed that PABPs have overlapping yet distinct expression patterns in mouse
The distinct structure of PABP5 suggested that its function may vary from PABP1.
Characterisation of its activities in translational regulation was therefore investigated.
When tethered to a reporter mRNA PABP5 had limited translational stimulatory
activity, and in addition could not be isolated via m7G cap chromatography and
failed to interact with translation initiation factors including eIF4G and PAIP-1.
These factors interact with PABP1 to positively promote translation, implying that
PABP5 function in translational regulation differs from other PABPs investigated. Examining why PABP5 failed to display translational stimulatory activity also
revealed an interaction with the negative regulator of translation, PAIP-2. In
summary, I present the first description of PABP5 cellular localisation, and have
gone some way towards elucidating the molecular function of this uncharacterised