{{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
A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs ( snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to specif ...
, the
protein complex
A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain.
Protein c ...
specialized for carrying out
RNA splicing
RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). It works by removing all the introns (non-coding regions of RNA) and ''splicing'' b ...
during the process of
post-transcriptional modification
Transcriptional modification or co-transcriptional modification is a set of biological processes common to most eukaryotic cells by which an RNA primary transcript is chemically altered following transcription from a gene to produce a mature, func ...
. The region is rich with
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 other ...
nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
s, especially
uracil
Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by ...
, 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., gene. ...
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
Polypyrimidine tract-binding protein, also known as PTB or hnRNP I, is an RNA-binding protein. PTB functions mainly as a splicing regulator, although it is also involved in alternative 3' end processing, mRNA stability and RNA localization. Two ...
'' (PTB), which plays a regulatory role in
alternative splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...
. 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 sequen ...
silencing, by which a particular exon region normally spliced into the mature mRNA is instead left out, resulting in the
expression
Expression may refer to:
Linguistics
* Expression (linguistics), a word, phrase, or sentence
* Fixed expression, a form of words with a specific meaning
* Idiom, a type of fixed expression
* Metaphorical expression, a particular word, phrase, o ...
of an
isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
of the protein for which the mRNA
codes
In communications and information processing, code is a system of rules to convert information—such as a letter, word, sound, image, or gesture—into another form, sometimes shortened or secret, for communication through a communication ...
. Because PTB is ubiquitously expressed in many higher
eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s, it is thought to suppress the inclusion of "weak" exons with poorly defined
splice site
RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). It works by removing all the introns (non-coding regions of RNA) and ''splicing'' ba ...
s.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 an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
and
skeletal muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
express alternate isoforms distinguished by mutually exclusive exon selection in alpha-
tropomyosin
Tropomyosin is a two-stranded alpha-helical, coiled coil protein found in actin-based cytoskeletons.
Tropomyosin and the actin skeleton
All organisms contain organelles that provide physical integrity to their cells. These type of organelles a ...
.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.