Central Dogma of Molecular Biology
70The central dogma of molecular biology refers to the flow of information from one form to another as it relates to the functioning of a cell. The flow follows this basic pattern: DNA to RNA to Protein, with some exceptions. Central to this flow are the intermediary steps of transcription (which occurs between the DNA and RNA) and translation (which occurs after the RNA is transcribed and results in a polypeptide).
In the nucleus, DNA is first transcribed into pre-mRNA. Firstly, a subunit of TFIID, TBP, binds to the “TATA” box near the initiation site of transcription. Other transcription factors subsequently attach, allowing the final attachment of RNA Polymerase. Finally, other minor transcription factors bind to finish the transcription complex, and ATP is hydrolyzed into ADP and Pi in an exergonic reaction that fuels the synthesis of pre-mRNA. RNA Polymerase synthesizes the pre-mRNA strand (using the DNA template) from the 5’ to 3’ end and then releases the RNA strand.
Before mRNA can leave the nucleus for the ribosome in the cytoplasm, pre-mRNA must first be processed so as to include a methylated cap and a polyadentylated tail. The methylated cap is actually added (on the 5’ end) to the pre-mRNA strand as soon as RNA Polymerase begins to transcribe. After the pre-mRNA is released, cleavage factors bind to specific sites on the RNA strand and prepare it for cleavage. Poly-A Polymerase then binds to and cleaves the 3’ end and synthesizes the polyadentylated tail, which consists of a repeating sequence of adenine bases. Along the tail proteins bind which accelerate the rate of Poly-A Polymerase.
After the methylated cap and poly-a tail are added to the pre-mRNA, splicing of introns and fusing of exons occurs. Introns, which are senseless and code for nothing, contain a GU and A site whereby the start and end (respectively) of an intron are thusly identified. The splicesosome, consisting of several different components, binds to the GU site and loops. Then, binding the GU site to the A site, the intron is spliced and the remaining exons are fused. Alternative splicing allows for the coding of multiple proteins from a single gene as, in this process, exons are ligated in different ways.
Now, the nascent mRNA travels to the ribosome for translation. Near the 5’ end of the mRNA, a small ribosomal subunit attaches and moves to the initiation site. tRNA binds to the AUG initiation codon (which codes for the amino acid methionine) with its complementary anticodon. The large ribosomal unit then binds and creates the P and A site. Alongside the methionine carrying tRNA in the P site, another tRNA binds to the A site and the P site tRNA (for methionine) transfers its amino acid to the A site tRNA. Then the ribosomal complex moves along the mRNA strand and the second tRNA (which should consist of two amino acids) moves into the P site and another tRNA moves into the A site, after which case the process repeats until the polypeptide (protein) is complete. Additional folding if necessary may occur at the ER or with the assistance of a chaperonin protein.
