Polypyrimidine tract
Encyclopedia
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
nucleotide
s, especially uracil
, and is usually 15-20 base pair
s long, located about 5-40 base pairs before the 3' end of the intron
to be spliced.
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 eukaryote
s, it is thought to suppress the inclusion of "weak" exons with poorly defined splice sites. However, PTB binding is not sufficient to suppress "robust" exons.
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
.
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
(mRNA) that promotes the assembly of the spliceosome
Spliceosome
A spliceosome is a complex of snRNA and protein subunits that removes introns from a transcribed pre-mRNA segment. This process is generally referred to as splicing.-Composition:...
, the protein complex
Protein complex
A multiprotein complex is a group of two or more associated polypeptide chains. If the different polypeptide chains contain different protein domain, the resulting multiprotein complex can have multiple catalytic functions...
specialized for carrying out RNA splicing
RNA splicing
In molecular biology and genetics, splicing is a modification of an RNA after transcription, in which introns are removed and exons are joined. This is needed for the typical eukaryotic messenger RNA before it can be used to produce a correct protein through translation...
during the process of post-transcriptional modification
Post-transcriptional modification
Post-transcriptional modification is a process in cell biology by which, in eukaryotic cells, primary transcript RNA is converted into mature RNA. A notable example is the conversion of precursor messenger RNA into mature messenger RNA , which includes splicing and occurs prior to protein synthesis...
. The region is rich with pyrimidine
Pyrimidine
Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...
nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
s, especially uracil
Uracil
Uracil is one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others are adenine, cytosine, and guanine. In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine.Uracil is a common and...
, and is usually 15-20 base pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
s long, located about 5-40 base pairs before the 3' end of the intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
to be spliced.
A number of protein factors bind to or associate with the polypyrimidine tract, including the spliceosome component U2AF and the polypyrimidine tract-binding protein
Polypyrimidine tract-binding protein
Polypyrimidine tract-binding protein is an RNA-binding protein, also known as PTB or hnRNP I. PTB functions mainly as a splicing regulator, although it is also involved in alternative 3' end processing, mRNA stability and RNA localization....
(PTB), which plays a regulatory role in alternative splicing
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
. PTB's primary function is in exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
silencing, by which a particular exon region normally spliced into the mature mRNA is instead left out, resulting in the expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
of an isoform of the protein for which the mRNA codes
Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....
. Because PTB is ubiquitously expressed in many higher eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s, it is thought to suppress the inclusion of "weak" exons with poorly defined splice sites. However, PTB binding is not sufficient to suppress "robust" exons.
The suppression or selection of exons is critical to the proper expression of tissue
Biological tissue
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
-specific isoforms. For example, smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
and skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
express alternate isoforms distinguished by mutually exclusive exon selection in alpha-tropomyosin
Tropomyosin
Tropomyosin is an actin-binding protein that regulates actin mechanics. It is important, among other things, for muscle contraction. Tropomyosin, along with the troponin complex, associate with actin in muscle fibers and regulate muscle contraction by regulating the binding of myosin...
.