Post-transcriptional Gene Regulation: Role of the Polypyrimidine Tract-binding Protein (PTB) and Associated Factors in "From the hallowed halls of Herpesvirology".

The overall processes of gene expression, from mRNA biogenesis to translation and degradation, require RNA messenger ribonucleoprotein (mRNP) complexes assembly, differentially combined with individual transcripts in order to mediate the post-transcriptional events. One of those events, the alternative splicing of pre-mRNA, is responsible for the wide variety and complexity levels of transcriptome and proteome. Large-scale expressed sequence tag and genome-wide analyses estimate that more than 60% of human genes undergo alternative splicing with a differential tissue distribution. More than 15% of human genetic diseases are associated to mutations in the consensus splice sites and disruption of splicing regulatory networks contributes to various diseases, including cancer. Among the best characterized splicing regulators is the polypyrimidine tract binding protein (PTB) and its paralog nPTB. Highly conserved in vertebrates, PTB has been implicated in several cellular process related to post-transcriptional regulation. In addition to the alternative splicing regulation, PTB is involved into polyadenylation, mRNA stability and initiation of translation. For the latter, several studies have described the PTB recruitment in IRES-mediated translation initiation or propagation of several viruses including hepatitis C virus and picornaviruses. To perform these functions PTB is regulated in its intracellular localization, shuttling between nucleus and cytoplasm. Tissue specific PTB isoforms and co-regulators, the ribonucleoproteins Raver 1 and 2, have been recently identified. Mechanisms of post-transcriptional regulation mediated by PTB, nPTB and Raver proteins are described in the present review.