Polypyrimidine tract

The polypyrimidine tract is a region of messenger RNA (mRNA) that promotes the assembly of the spliceosome, the protein complex specialized for carrying out RNA splicing during the process of post-transcriptional modification. The region is rich with pyrimidine nucleotides, especially uracil, and is usually 15-20 base pairs long, located about 5-40 base pairs before the 3' end of the intron to be spliced.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.]

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.Wagner EJ, Garcia-Blanco MA. (2001). Polypyrimidine tract binding protein antagonizes exon definition. "Mol Cell Biol" 21(10):3281-3288.] However, PTB binding is not sufficient to suppress "robust" exons.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.]

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.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.]

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