Transcription preinitiation complex
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The preinitiation complex (abbreviated PIC) is a complex of approximately 100
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s that is necessary for the
transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...
of protein-coding
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s in
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 and
archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
. The preinitiation complex positions
RNA polymerase II RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukaryo ...
at gene
transcription start site Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules calle ...
s, denatures the DNA, and positions the DNA in the RNA polymerase II
active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...
for transcription. The minimal PIC includes RNA polymerase II and six
general transcription factor General transcription factors (GTFs), also known as basal transcriptional factors, are a class of protein transcription factors that bind to specific sites ( promoter) on DNA to activate transcription of genetic information from DNA to messenger ...
s: TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH. Additional regulatory complexes (such as the mediator coactivator and
chromatin remodeling Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out ...
complexes) may also be components of the PIC.


Assembly

A classical view of PIC formation at the promoter involves the following steps: *
TATA binding protein The TATA-binding protein (TBP) is a general transcription factor that binds specifically to a DNA sequence called the TATA box. This DNA sequence is found about 30 base pairs upstream of the transcription start site in some eukaryotic gene p ...
(TBP, a subunit of TFIID) binds the promoter, creating a sharp bend in the promoter DNA. ** Animals have some TBP-related factors (TRF;
TBPL1 TATA box-binding protein-like protein 1 is a protein that in humans is encoded by the ''TBPL1'' gene. Function Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates ...
/ TBPL2). They can replace TBP in some special contexts. * TBP recruits TFIIA, then TFIIB, to the promoter. * TFIIB recruits RNA polymerase II and TFIIF to the promoter. * TFIIE joins the growing complex and recruits TFIIH which has protein kinase activity (phosphorylates RNA polymerase II within the CTD) and DNA helicase activity (unwinds DNA at promoter). It also recruits nucleotide-excision repair proteins. * Subunits within TFIIH that have ATPase and
helicase Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separatin ...
activity create negative superhelical tension in the DNA. * Negative superhelical tension causes approximately one turn of DNA to unwind and form the
transcription bubble A transcription bubble is a molecular structure formed during DNA transcription when a limited portion of the DNA double helix is unwound. The size of a transcription bubble ranges from 12-14 base pairs. A transcription bubble is formed when the ...
. * The template strand of the transcription bubble engages with the RNA polymerase II active site. * RNA synthesis begins. * After synthesis of ~10 nucleotides of RNA, and an obligatory phase of several abortive transcription cycles, RNA polymerase II escapes the promoter region to transcribe the remainder of the gene. An alternative hypothesis of PIC assembly postulates the recruitment of a pre-assembled "
RNA polymerase II holoenzyme 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 ...
" directly to the promoter (composed of all, or nearly all GTFs and RNA polymerase II and regulatory complexes), in a manner similar to the bacterial RNA polymerase (RNAP).


Other preinitiation complexes

Archaea have a preinitiation complex resembling that of a minimized Pol II PIC, with a TBP and an
Archaeal transcription factor B Archaeal transcription factor B (ATFB or TFB) is a protein family of extrinsic transcription factors that guide the initiation of RNA transcription in organisms that fall under the domain of Archaea. It is homologous to eukaryotic TFIIB and, mo ...
(TFB, a TFIIB homolog). The assembly follows a similar sequence, starting with TBP binding to the promoter. An interesting aspect is that the entire complex is bound in an inverse orientation compared to those found in eukaryotic PIC. They also use TFE, a TFIIE homolog, which assists in transcription initiation but is not required. Pol I initiation start with
UBTF Nucleolar transcription factor 1 is a protein that in humans is encoded by the ''UBTF'' gene. Function Upstream binding factor (UBF) is a transcription factor required for expression of the 18S, 5.8S, and 28S ribosomal RNAs, along with SL1 (a c ...
(UBF) recognizing an upstream control element (UCE) located around ~100 to 200 bp upstream. It recruits
Selective factor 1 Selective factor 1 (also known as SL1) is a transcription factor that binds to the gene promoter, promoter of genes and recruits a preinitiation complex to which RNA polymerase I will bind to and begin the transcription of ribosomal RNA (rRNA). ...
(TIF-IB), which is a complex of TBP and three units of
TBP-associated factor The TBP-associated factors (TAF) are proteins that associate with the TATA-binding protein in transcription initiation. It is a part of the transcription initiation factor TFIID multimeric protein complex. It also makes up many other factors, incl ...
. UBF then recognizes the core control elements. Phosphorylated RRN3 (TIF-IB) binds Pol I. The entire complex recognizes UBF/SL1, binds to it, and starts transcribing. The precise usage of subunits differ among organisms. Pol III has three classes of initiation, which start with different factors recognizing different control elements but all converging on TFIIIB (similar to TFIIB-TBP; consists of TBP/TRF, a TFIIB-related factor, and a B″ unit) recruiting the Pol III preinitiation complex. The overall architecture resembles that of Pol II. Only TFIIIB needs to remain attached during elongation.


References


External links

*Descriptive image â€
biochem.ucl.ac.uk
{{Transcription Gene expression