Poly(A)-binding protein

[4] The binding protein is also involved in mRNA precursors by helping polyadenylate polymerase add the poly(A) nucleotide tail to the pre-mRNA before translation.

[5] The nuclear isoform selectively binds to around 50 nucleotides and stimulates the activity of polyadenylate polymerase by increasing its affinity towards RNA.

Poly(A)-binding protein is also present during stages of mRNA metabolism including nonsense-mediated decay and nucleocytoplasmic trafficking.

[6] Cytosolic poly-A binding protein (PABPC) is made up of four RNA recognition motifs (RRMs) and a C-terminal region known as the PABC domain.

Previous solution NMR and X-ray crystallography studies have shown that RRMs are globular domains, each composed of 4 anti-parallel β sheets that are backed by 2 α-helices.

The central two β-strands, connected by a short linker, of each RRM forms a trough-like surface that is thought to be responsible for binding to the poly(A) oligonucleotides.

This interaction enhances both the affinity of eIF4E for the cap structure and PABP1 for poly(A), effectively locking proteins onto both ends of the mRNA.

As a result, this association may in part underlie the ability of PABP1 to promote small ribosomal (40S) subunit recruitment, which is aided by the interaction between eIF4G and eIF3.

Alternatively, it may link translation to mRNA decay, as eRF3 appears to interfere with the ability of PABP1 to multimerise/form on poly(A), potentially leading to PABP1 dissociation, deadenylation and, ultimately, turnover.

[15] Mutations in PABPN1 that cause this disorder, result when the protein has an extended polyalanine tract (12-17 alanines long vs. the expected amount of 10).

In recent studies on OPMD in Drosophila, it has been shown that the degeneration of muscles within those who are affected may not solely be due to the expanded polyalanine tract.

Trehalose is a special form of sugar that has shown reduced aggregate formation and delayed pathology in the mouse model of OPMD.

Doxycycline also played a similar role in delaying toxicity of OPMD in mouse models most likely due to stopping aggregate formation and reduced apoptosis.