Transcription preinitiation complex
Encyclopedia
The preinitiation complex (abbreviated PIC) is a large complex of protein
s that is necessary for the transcription
of protein-coding gene
s in eukaryote
s (+archaea
). The preinitiation complex helps position RNA polymerase II
over gene transcription start sites, denatures the DNA
, and positions the DNA in the RNA polymerase II active site
for transcription.
Typically the PIC is made up of six general transcription factor
s: TFIIA, TFIIB
, TFIID
, TFIIE
, TFIIF
, and TFIIH
.
proposed the following model of the PIC at promoters with TATA boxes:
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s that is necessary for the transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
of protein-coding gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s in 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 (+archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...
). The preinitiation complex helps position RNA polymerase II
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
over gene transcription start sites, denatures the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, and positions the DNA in the RNA polymerase II active site
Active site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...
for transcription.
Typically the PIC is made up of six general transcription factor
General transcription factor
General transcription factors or basal transcription factors are protein transcription factors that have been shown to be important in the transcription of class II genes to mRNA templates...
s: TFIIA, TFIIB
Transcription Factor II B
Transcription factor II B is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. It is encoded by the gene....
, TFIID
Transcription Factor II D
RNA polymerase II holoenzyme is a form of eukaryotic RNA polymerase II that is recruited to the promoters of protein-coding genes in living cells. It consists of RNA polymerase II, a subset of general transcription factors, and regulatory proteins known as SRB proteins...
, TFIIE
Transcription Factor II E
Transcription factor II E is one of several general transcription factors that make up the RNA polymerase II preinitiation complex.Transcription Factor II E is encoded by the GTF2E1 and GTF2E2 genes. TFIIE is thought to be involved in DNA melting at the promoter: it contains a zinc ribbon motif...
, TFIIF
Transcription Factor II F
Transcription factor II F is one of several general transcription factors that make up the RNA polymerase II preinitiation complex.Transcription Factor II F is encoded by the , , and genes. DNA is thought to be wrapped one complete turn around the preinitiation complex and it is TFIIF that...
, and TFIIH
Transcription Factor II H
Transcription factor II H is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. TFIIH consists of ten subunits, 7 of which form the core complex...
.
Assembly
In 2007 Roger D. KornbergRoger D. Kornberg
Roger David Kornberg is an American biochemist and professor of structural biology at Stanford University School of Medicine.Kornberg was awarded the Nobel Prize in Chemistry in 2006 for his studies of the process by which genetic information from DNA is copied to RNA, "the molecular basis of...
proposed the following model of the PIC at promoters with TATA boxes:
- TATA binding proteinTATA Binding ProteinThe TATA-binding protein is a general transcription factor that binds specifically to a DNA sequence called the TATA box. This DNA sequence is found about 35 base pairs upstream of the transcription start site in some eukaryotic gene promoters...
(TBP, a subunit of TFIID) binds the promoter, creating a sharp bend in the DNA. This bend wraps the DNA around RNA polymerase II and the C-terminal domain of TFIIB. TBP binds the TATA boxTATA boxThe TATA box is a DNA sequence found in the promoter region of genes in archaea and eukaryotes; approximately 24% of human genes contain a TATA box within the core promoter....
, and the spacing of the TATA box relative to the transcription start site (25-30 base pairBase pairIn 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 upstream of the transcription start site) ensures that RNA polymerase II will be properly positioned. - The N-terminal domain of TFIIB brings the DNA into proper position for entry into the active siteActive siteIn biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...
of RNA polymerase II. - TFIIE joins the growing complex and recruits TFIIH.
- Subunits within TFIIH that have ATPaseATPaseATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...
and helicaseHelicaseHelicases are a class of enzymes vital to all living organisms. They are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two annealed nucleic acid strands using energy derived from ATP hydrolysis.-Function:Many cellular processes Helicases are a...
activity create negative superhelicalDNA supercoilDNA supercoiling refers to the over- or under-winding of a DNA strand, and is an expression of the strain on the polymer. Supercoiling is important in a number of biological processes, such as compacting DNA. Additionally, certain enzymes such as topoisomerases are able to change DNA topology to...
tension in the DNA. - Negative superhelical tension causes the DNA to denature and form the transcription bubbleTranscription bubbleA transcription bubble is a molecular structure that occurs during the transcription or replication of DNA when DNA helicase and DNA topoisomerase "unzip" the DNA double strand. DNA polymerase or RNA polymerase may then bind to the exposed DNA and begin synthesizing a new strand of DNA or RNA...
. TFIIF binds to the coding strand of the single-stranded, denatured DNA and keeps the bubble open. - The single-stranded non-coding strand of the DNA can then bend and enter the RNA polymerase II active site.
- If transcription proceeds more than six bases, TFIIB is displaced and RNA polymerase II escapes the promoter region to transcribe the remainder of the gene.
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