Gene expression is a fundamental process in all living organisms, allowing the information encoded in DNA to be utilized for cellular functions. This intricate process begins with transcription, where a specific segment of DNA is copied into an RNA molecule. General transcription factors (GTFs) are molecular facilitators universally required for the initiation of transcription for most genes. These proteins are indispensable components that ensure the accurate and efficient start of this genetic information transfer.
Defining General Transcription Factors
General transcription factors are a distinct class of proteins that play a foundational role in initiating transcription by RNA polymerase II in eukaryotic cells. They are essential for the transcription of nearly all protein-coding genes. These factors assemble at specific DNA sequences called promoters to activate the copying of genetic information from DNA into messenger RNA.
The main general transcription factors include TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH. This set of proteins forms a complex assembly at the promoter region of a gene. Unlike regulatory transcription factors that modulate the rate of transcription in a gene-specific manner, GTFs provide the core machinery required for the basic act of transcription. GTFs are highly abundant and necessary for the expression of a vast majority of protein-coding genes, while regulatory factors are numerous and allow for precise control over individual genes.
The Orchestrated Process of Transcription Initiation
Transcription initiation is a highly coordinated process involving the sequential assembly of general transcription factors and RNA polymerase II to form a pre-initiation complex (PIC) at the gene’s promoter. This assembly begins with TFIID, the first general transcription factor to bind to the promoter. TFIID is composed of the TATA-binding protein (TBP) and several TBP-associated factors (TAFs), which recognize specific DNA sequences within the promoter, such as the TATA box, typically found about 25 to 35 base pairs upstream of the transcription start site. TFIID acts as a crucial scaffold for the subsequent recruitment of other components.
Following TFIID’s binding, TFIIA joins the complex, interacting with TBP within TFIID. TFIIA helps to enhance and stabilize TFIID’s binding to the promoter DNA. Its presence contributes to the overall stability of the forming pre-initiation complex. Next, TFIIB binds to the TFIID-DNA complex, serving as a crucial bridge. TFIIB recognizes a specific DNA sequence called the B recognition element (BRE) within the promoter, and its binding is important for recruiting RNA polymerase II and influencing the precise transcription start site.
RNA polymerase II, the enzyme responsible for synthesizing RNA, is then recruited to the promoter, often in conjunction with TFIIF. TFIIF associates with RNA polymerase II, helping to prevent its non-specific binding to DNA outside the promoter region. This factor also stabilizes the interaction between RNA polymerase II, TBP, and TFIIB, correctly positioning the polymerase at the start site. The final general transcription factors to join the complex are TFIIE and TFIIH. TFIIE’s role includes recruiting TFIIH to the initiation complex.
TFIIH is a multi-subunit complex with distinct enzymatic activities essential for transcription initiation. It contains helicase subunits, XPB and XPD, that unwind the DNA double helix at the transcription start point. This unwinding creates a transcription bubble, providing RNA polymerase II access to the DNA template strand for RNA synthesis.
Additionally, TFIIH possesses kinase activity, primarily through its CDK7 subunit. This kinase phosphorylates the C-terminal domain (CTD) of RNA polymerase II on specific serine residues. This phosphorylation event is a key signal that triggers RNA polymerase II to disengage from the promoter and begin the elongation phase of transcription, where the RNA chain is synthesized.
The Essential Role of General Transcription Factors
General transcription factors are fundamental components for RNA polymerase II-mediated transcription in eukaryotic cells. Their coordinated actions form the basic machinery that enables the expression of protein-coding genes. Without the precise and sequential assembly and functions of these factors, RNA polymerase II would be unable to accurately or efficiently initiate the process of transcription. These factors are universally required across various cell types and organisms for the basic act of gene expression, making it possible for cells to read and implement their genetic instructions.