Genetic code

The genetic code is the universal language that dictates how the information stored in DNA is converted into proteins through a two-step process known as the Central Dogma:

• 1st step: DNA is first transcribed into messenger RNA (mRNA) and mRNAs get transported out of the nucleus into the cytoplasm. These mRNAs are working copies of the gene.

• 2nd step: mRNA is then translated into protein as ribosomes read off the mRNAs.

Proteins are synthesized by ribosomes, serving as the final expression of genetic information encoded in genes.

This translation relies on the triplet code, wherein every three-nucleotide sequence, known as a codon, specifies either an amino acid or a signal for the initiation or termination of protein synthesis.

During translation, each codon on the mRNA pairs with a corresponding anticodon on transfer RNA (tRNA) in a process known as the codon-anticodon relationship. This interaction ensures that the correct amino acid is added to the growing polypeptide chain. Notably, the genetic code is described as degenerate, meaning that most amino acids are encoded by more than one codon. This redundancy is partly due to wobble pairing, which allows a flexible match between the third nucleotide of the codon and the corresponding nucleotide of the anticodon, thereby permitting slight variations without altering the amino acid that is incorporated.

The translation process begins with an initiation codon—typically AUG, which codes for methionine—that signals the start of protein synthesis. As the ribosome moves along the mRNA, codons are read sequentially, and specific amino acids are joined together to form a protein.

Errors in this process can result in different types of mutations:

• a missense mutation occurs when a codon is altered such that it codes for a different amino acid
• a nonsense mutation converts a codon into a stop signal, leading to premature termination of protein synthesis.

Finally, translation concludes when a termination codon (UAA, UAG, or UGA) is encountered, signaling the end of the polypeptide chain.

Messenger RNA (mRNA) structure and composition

• Messenger RNA (mRNA) serves as the intermediary between DNA transcription and protein translation, carrying genetic instructions from the nucleus (or nucleoid in prokaryotes) to the ribosomes. It is composed of RNA nucleotides arranged in a sequence that corresponds to the coding region of a gene.

Structural features of mRNA

Eukaryotic mRNA

In eukaryotic cells, mRNA undergoes extensive post-transcriptional modifications to ensure stability and efficient translation. These modifications include:

• 5’ Cap: A specially modified guanine nucleotide is added to the 5’ end through an unusual linkage. This 5’ cap serves multiple purposes:
  • Protects the mRNA from degradation by exonucleases
  • Facilitates ribosomal recognition and translation initiation
• Poly-A Tail: The 3’ end of mRNA is extended with a polyadenine (poly-A) tail, consisting of multiple adenine (A) residues. This structure:
  • Shields the mRNA from degradation
  • Aids in mRNA export from the nucleus and enhances translation efficiency

The typical structure of a eukaryotic mRNA molecule can be summarized as:
5’ Cap - Coding Sequence - 3’ Poly-A Tail

Prokaryotic mRNA

Unlike eukaryotic mRNA, prokaryotic mRNA lacks both a 5’ cap and a poly-A tail. Instead, bacterial mRNAs are often translated while transcription is still occurring, a process known as coupled transcription and translation.

mRNA levels and gene expression

The abundance of mRNA in a cell is directly correlated with protein synthesis levels—higher mRNA expression results in increased protein production. Several factors influence mRNA levels:

• Promoter Strength: A strong promoter leads to higher transcription rates, producing more mRNA.
• DNA and Histone Methylation: In eukaryotes, DNA methylation and histone modifications play a key role in regulating transcription. Less methylation typically results in greater gene expression, leading to more mRNA production.