LifeLine

Ever wondered how the instructions in your DNA actually turn into proteins? From your eye color to skin repair, it all comes down to the central dogma. The central dogma describes the flow of genetic information in living organisms. The flow is: DNA → RNA → Proteins.

DNA controls the production of proteins in a cell. These proteins are specific to each type and functionality of cell. Proteins are everything, they build muscles, digest food, carry oxygen, fight infection etc. If there is a mutation in the DNA, the protein may be faulty and can cause diseases such as sickle cell anemia. 

DNA is bound in the nucleus, and ribosomes are responsible for synthesising proteins. But ribosomes are present in the cytoplasm. Therefore, DNA must communicate with ribosomes through RNA. The 1st step in this process is Transcription.

Transcription

In the nucleus, the gene (a section of DNA coding for a polypeptide) is “read” and synthesized into messenger RNA (mRNA). The initiation for transcription is done by RNA polymerase, which unwinds the DNA helix. Then, RNA polymerase slides over the DNA until it finds the promoter sequence (AT nucleotide-rich sequence). Next, the ribonucleotides are activated by the addition of inorganic phosphate. After, the sigma factor promotes RNA polymerase to start the process. The transcription bubble is now open, and replication starts. The ribonucleotides join the mRNA transcript. It is also important to note polymerase enzyme can only work in the 5’ → 3’ direction, so the DNA strand should be antiparallel (3’ → 5’). Only 1 strand will take part in transcription; otherwise, there would be antiparallel bonding, making the mRNA useless for protein synthesis. The mRNA is complementary (similar) to the non-coding strand; hence, it is known as the sense strand. Conversely, the mRNA is antiparallel to the template strand, hence, the antisense strand. Once mRNA has been synthesized, meaning the gene has been coded, the mRNA detaches and the transcription bubble closes. The ending factor is known as the Rho factor. This is the end of transcription

Post-Transcription Modification 

Once transcription is over, there needs to be modification to the mRNA before entering the cytoplasm to protect and stabilize the mRNA strand from degradation. Post-modification, the strand is referred to as mature mRNA. To begin with, the first modification is capping of the 5’ end to ensure nothing slides over the mRNA. The capping of the 5’ end is done with guanine-rich nucleotides, which are methylated. Afterwards, there is a long poly A-tail added to the 3’ end, which is referred to as tailing of the 3’ end. Below is a picture of a mature mRNA strand. Finally, the last step for modification is the splicing of introns. DNA has abundant non-coding regions that cannot be expressed as proteins; these are known as introns. Once the introns are spliced, the mRNA strand will only consist of exons. The mRNA is now ready to be moved out of the nucleus for translation.

Translation

Translation is the synthesis of a polypeptide chain from the mature mRNA. This process occurs in the cytoplasm. Before we begin, let’s differentiate between the RNAs involved in the process. 

1. mRNA (messenger RNA) → carries the message from DNA to ribosomes
2. tRNA (transfer RNA) → carries a specific amino acid for translation
3. rRNA (ribosomal RNA) → genetic material for ribosomes

The start codon for translation is AUG, and the 3 stop codons are UAA, UAG, UGA. DNA is degenerative, meaning that 1 amino acid can be coded by x no. of codons. This genetic code is read in triplets. There are a total of 21 amino acids and 64 codons. 

Firstly, translation begins with the activation of amino acids. Each amino acid binds to the 3’ end of a specific tRNA using ATP. Secondly, the mature mRNA is read by the smaller subunit of ribosomes. Translation will only initiate when the small subunit encounters the initiation codon, AUG. Once it is encountered, the large subunit covers the tRNA. Ribosomes have 3 sites: 

active (A) → tRNA anticodon loop binds with the codon of mRNA

peptidyl (P) → peptide bond between 2 amino acids of tRNA

exit (E) → discharges tRNA which lost the amino acid

This ribosome slides over the mRNA, and the initiation codon will be read, then the next triplet is read, and the initiation codon will move to the P site. The active site becomes available for the next triplet. Then, there is a condensation reaction with the initiation codon amino acid and 2nd tRNA amino acid. Finally, the exit site removes the discharged initiation codon, the active site becomes available again, and the peptidyl site undergoes peptide bonding. This process will continue, referred to as elongation. The amino acid will be delivered by a specific tRNA to the ribosomes. The polypeptide chain will be synthesized and continue to grow until the stop codon is encountered. This is the termination of translation. 

In conclusion, in the central dogma, DNA is transcribed into mRNA, which is then translated into proteins. These proteins are essential molecules that then carry out nearly every function in our body. Did you know that only 1-2% of our DNA is actually synthesized into proteins? The beauty of the central dogma lies in its simplicity and its universality. It’s a process shared by almost all living organisms. This isn’t just a biological process, but rather a language through which life expresses itself.