Protein biosynthesis and genetic code

Gene expression and cell differentiation

Cells of a multicellular organism perform diverse functions owing to differential gene expression. At different stages of ontogenesis and in various parts of the embryo, strictly defined regions of DNA are activated.

The realization chain operates as follows: the activation of a structural gene leads to the synthesis of a specific mRNA, which serves as a template for assembling a unique protein. It is this protein that determines cell specialization and the formation of a specific trait. The cell tightly controls this process at multiple levels: during transcription (selecting what to transcribe), at the translation stage, and during post-translational modifications.

Transcription and RNA processing

Transcription is the copying of the genetic code from DNA to RNA. The process is mediated by RNA polymerase enzymes. Eukaryotes have three types of them, each responsible for a specific type of RNA (for example, polymerase I synthesizes rRNA, II — mRNA, III — tRNA).

Synthesis goes through three stages:

1. Initiation: binding of the enzyme to the starting site (promoter).
2. Elongation: sequential extension of the RNA chain.
3. Termination: cessation of assembly at a specialized region (terminator).

In eukaryotes, the resulting pre-mRNA is not ready for function and undergoes processing (maturation):

• Capping: 7-methylguanosine is attached to the 5'-end to protect the molecule and initiate subsequent protein assembly.
• Polyadenylation: a poly-A tail is attached to the 3'-end, providing the molecule with stability.
• Splicing: enzymes excise non-coding regions (introns) and ligate the coding regions (exons).

Translation: from nucleotides to amino acids

Translation takes place in the cytoplasm. Here, the mRNA nucleotide sequence is translated into an amino acid sequence. The process requires mature mRNA, small and large ribosomal subunits, transfer RNAs (carrying an amino acid and an anticodon), aminoacyl-tRNA synthetase enzymes, as well as ATP and GTP energy.

Stages of translation:

• Initiation: the ribosome assembles on the start codon AUG.
• Elongation: cyclical addition of new amino acids with the formation of peptide bonds.
• Termination: one of the stop codons (UAA, UAG, or UGA) enters the A-site of the ribosome, after which the completed polypeptide is released and the complex dissociates.

Features of viral reproduction

Viruses synthesize their components via a disjunctive (compartmentalized) pathway — nucleic acids and proteins are manufactured in different cellular structures. The strategy depends on the genome type:

• DNA-containing viruses: the classical pathway from DNA to mRNA and protein. Transcription and replication occur in the nucleus, and progeny DNA egresses into the cytoplasm by budding. An exception is the poxvirus, whose transcription occurs in the cytoplasm utilizing its own polymerase.
• Positive-sense RNA viruses: their RNA functions directly as ready mRNA. Translation yields a long polypeptide, which is cleaved by proteases into the required functional proteins.
• Negative-sense RNA viruses: first, short and full-length positive-sense RNAs are synthesized using virion polymerase-transcriptase, and only from these templates is the protein translated or the genome copied.
• Retroviruses: utilize the enzyme reverse transcriptase for reverse transcription (RNA → DNA). The resulting DNA integrates into the host cell genome, after which cellular RNA polymerase synthesizes viral mRNAs.

Class and exam questions

What else to study on this topic

• Mechanisms of transcription regulation: the role of promoters and terminators
• Post-translational modification of proteins (expression)
• Function of aminoacyl-tRNA synthetases and the energy balance of translation
• Features of replication and transcription in retroviruses (action of reverse transcriptase)
• Mechanisms of DNA virus budding through the nuclear membrane

Other topics in the "Additional Topics" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.