New Insights into Functional Roles of the Polypyrimidine Tract-Binding Protein

Abstract

Polypyrimidine Tract Binding Protein (PTB) is an intensely studied RNA binding protein involved in several post-transcriptional regulatory events of gene expression. Initially described as a pre-mRNA splicing regulator, PTB is now widely accepted as a multifunctional protein shuttling between nucleus and cytoplasm. Accordingly, PTB can interact with selected RNA targets, structural elements and proteins. There is increasing evidence that PTB and its paralog PTBP2 play a major role as repressors of alternatively spliced exons, whose transcription is tissue-regulated. In addition to alternative splicing, PTB is involved in almost all steps of mRNA metabolism, including polyadenylation, mRNA stability and initiation of protein translation. Furthermore, it is well established that PTB recruitment in internal ribosome entry site (IRES) activates the translation of picornaviral and cellular proteins. Detailed studies of the structural properties of PTB have contributed to our understanding of the mechanism of RNA binding by RNA Recognition Motif (RRM) domains. In the present review, we will describe the structural properties of PTB, its paralogs and co-factors, the role in post-transcriptional regulation and actions in cell differentiation and pathogenesis. Defining the multifunctional roles of PTB will contribute to the understanding of key regulatory events in gene expression.

Novel RNA-binding Protein P311 Binds Eukaryotic Translation Initiation Factor 3 Subunit b (eIF3b) to Promote Translation of Transforming Growth Factor β1-3 (TGF-β1-3)

“…Our studies, however, revealed no P311 interaction or competition with either of them, indicating that the RRM region of eIF3b has multiple binding partners. RRM-containing genes represent about 0.5-1% of all human genes (67). Therefore, if the RRM represents the only P311 binding motif in the context of mRNA translation, the number of transcripts regulated by P311 should be relatively small.…”

Specificity and nonspecificity in RNA–protein interactions

“…A modular protein architecture can also enable proteins to recognize non-contiguous sequences 23 and thus intervening RNA sequences can become important contributors to specificity 107–109 . In addition, protein regions that link different RDBs can further modulate the contribution of each RBD to the protein’s overall RNA binding and specificity, and even promote cooperativity between RBDs 110 . Multiple RBDs with different inherent affinity distributions can also compensate for each other in a given protein and lead to uniform binding of an RBP to a wide range of diverse substrates (Fig.…”

Regulation of alternative splicing in Drosophila by 56 RNA binding proteins

“…EIF3GA is orthologous to human EIF3G, a component of the eIF3 complex involved in translation (Lasko 2000;Hinnebusch 2006). Many splicing regulators have been shown to also affect translation (e.g., Romanelli et al 2013;Maslon et al 2014); therefore, other examples of multifunctional RNA binding proteins exist. SHEP is an RNA binding protein that contains two RRM domains, is highly expressed in the nervous system of the fly (Brown et al 2014), and is involved in gravity sensing (Armstrong et al 2006).…”