{{Short description, A pyrimidine-rich sequence involved in pre-messenger RNA maturation
The polypyrimidine tract is a region of pre-messenger RNA (mRNA) that promotes the assembly of the spliceosome, the
protein complex
A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multidomain enzymes, in which multiple active site, catalytic domains are found in a single polypeptide chain.
...
specialized for carrying out
RNA splicing
RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcription (biology), transcript is transformed into a mature messenger RNA (Messenger RNA, mRNA). It works by removing all the introns (non-cod ...
pyrimidine
Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The oth ...
nucleotide
Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
s, especially
uracil
Uracil () (nucleoside#List of nucleosides and corresponding nucleobases, symbol U or Ura) is one of the four nucleotide bases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via ...
, and is usually 15–20
base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
s long, located about 5–40 base pairs before the 3' end of the
intron
An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...
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
Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...
. PTB's primary function is in
exon
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...
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
eukaryote
The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
s, 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
Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...
and
skeletal muscle
Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...
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.