A number of protein factors bind to or associate with the polypyrimidine tract, including the spliceosome component U2AF and the polypyrimidine tract-binding protein (PTB), which plays a regulatory role in alternative splicing. PTB's primary function is in exon silencing, by which a particular exon region normally spliced into the mature mRNA is instead left out, resulting in the expression of an isoform of the protein for which the mRNA codes. Because PTB is ubiquitously expressed in many higher eukaryotes, it is thought to suppress the inclusion of "weak" exons with poorly defined splice sites.[2] However, PTB binding is not sufficient to suppress "robust" exons.[3]
The suppression or selection of exons is critical to the proper expression of tissue-specific isoforms. For example, smooth muscle and skeletal muscle express alternate isoforms distinguished by mutually exclusive exon selection in alpha-tropomyosin.[4]
References
^Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J. (2004). Molecular Cell Biology. WH Freeman: New York, NY. 5th ed.
^Gooding C, Roberts GC, Smith CW. (1998). Role of an inhibitory pyrimidine element and polypyrimidine tract binding protein in repression of a regulated alpha-tropomyosin exon. RNA 4:85-100.
^Gooding C, Roberts GC, Moreau G, Nadal-Ginard B, Smith CW. (1994). Smooth muscle-specific switching of alpha-tropomyosin mutually exclusive exon selection by specific inhibition of the strong default exon. EMBO J 13(16):3861-72.