Expression of genes

• DNA serves two major functions:
1. Encoding structural information   that can be converted into RNA and (usually), hence into protein sequence.
2. Encoding regulatory signals   that allow certain proteins to decide where to begin or terminate reading DNA
• The "central dogma" of molecular biology: information flows from nucleic acids to proteins, not the reverse:

          DNA ----> RNA ----> polypeptides (proteins)
          Transcription = the process of making RNA from DNA templates

• Translation = the process of making polypeptides

Transcription

• Transcription is a fundamental cellular process: RNA polymerases "transcribe" the genetic information on DNA into RNA strands. All cells have RNA polymerases (RNAP).
  
  
• The RNA polymerases increase in complexity as you go from viruses (example, T7 RNA polymerase is made up of a single protein), to bacterial systems (one RNA polymerase made up of the proteins - beta, beta', 2 x alpha, omega and the sigma factor), and finally to eukaryotic systems (Three RNA polymerases - Pol I, Pol II, and Pol III, each with ten or more subunits).
  
  
• While the RNA polymerases have become increasing complex as life evolved, their overall structure (as evidenced by crystallographic structures of bacterial RNA polymerase and Pol II) show remarkable similarity. There is also sequence similarity between the bacterial polymerase protein subunits and the proteins that make up the eukaryotic polymerases.
  
  
• Transcription of any gene usually involves three distinct stages:
• First, the RNA polymerase has to find the start site of a gene. The "holoenzyme" form of the polymerase does this by looking for the "promoter" site that exists just upstream of the gene start site. This process is termed "transcription initiation". This is followed by opening up (melting) of the duplex DNA to form an "open complex".
  
  
• This is followed by a rapid change into the "elongation" phase of transcription where the "core polymerase" part of the RNA polymerase rapidly transcribes an RNA strand that is complementary to the "template" strand of the DNA. The change into the elongation phase usually occurs after a few bases of RNA have been transcribed (typically about 8-9 bases of RNA in bacterial system which form a RNA-DNA hybrid with the template strand), and involves a "clamping down" on the DNA to prevent the polymerase from falling off the DNA.
  
  
• The final stage of the transcription of a gene is "termination", after the stop codon of the gene. The process of termination usually involves sequences where the polymerase slows down or stalls, and the polymerase-RNA-DNA complex (often proteins such as rho and Nu­sA are involved in bacterial systems).
• Genes have to be transcribed to mRNAs before they can be translated into proteins; more or less mRNA from a particular gene equals more or less of the protein encoded by the gene. Transcription is, thus, an important point in the control of gene "expression". Most genes are controlled transcriptionally, usually by regulation of the level of transcriptional initiation. For example, if a gene has a strong promoter, it will be more highly expressed when compared to another gene with a weak promoter site. Similarly if a regulatory protein can bind the promoter site of a gene (and prevent transcription initiation), then it can turn off the expression of that gene.
  
  
• Transcriptional control of genetic expression is vital for cellular functions, and many diseases and cancers are results of defects in the transcriptional control of essentials genes.