Proteins are essential biological molecules that perform a vast array of functions crucial for life, from catalyzing biochemical reactions and transporting molecules to providing structural support and mediating cell signaling.
The precise mechanisms underlying protein synthesis are, therefore, of paramount importance. These mechanisms include sequential steps that translate the genetic information encoded within DNA into functional proteins, ultimately bridging the gap from genotype to phenotype.
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The Central Dogma of Molecular Biology
The Central Dogma of Molecular Biology articulates the unidirectional flow of genetic information within biological systems: DNA → RNA → Protein.
This fundamental principle underscores the primacy of DNA as the repository of heritable information, which is transcribed into messenger RNA (mRNA) molecules. These mRNA transcripts then serve as the template for protein synthesis, a process known as translation.
While the core process of translation is conserved across all organisms, notable differences exist between prokaryotic and eukaryotic protein synthesis. Prokaryotic translation often occurs concurrently with transcription due to the absence of a nucleus, allowing ribosomes to bind to nascent mRNA transcripts immediately.
In contrast, eukaryotic transcription and translation are spatially and temporally separated, with transcription occurring in the nucleus and translation in the cytoplasm. Eukaryotic mRNAs also undergo post-transcriptional modifications, including splicing and polyadenylation, which are absent in prokaryotes.
What Are the Phases of Mitosis?
Transcription: From DNA to mRNA
Transcription is a tightly regulated event crucial for gene expression. This process can be broadly divided into three distinct stages: initiation, elongation, and termination.
Initiation
Transcription initiation begins with the binding of RNA polymerase, a multi-subunit enzyme, to a specific DNA sequence called the promoter region. Prokaryotic promoters typically contain a Pribnow box, a sequence of ten base pairs upstream from the site of initiation of transcription (i.e., a -10 sequence), and a -35 sequence, which are recognized by the sigma factor subunit of RNA polymerase.
In eukaryotes, promoter regions are more complex and often include a TATA box, a CAAT box, and GC-rich sequences. Eukaryotic transcription initiation also requires the assembly of a pre-initiation complex involving RNA polymerase II and various transcription factors at the promoter.
Once bound, RNA polymerase unwinds a short stretch of DNA, forming a transcription bubble, and begins synthesizing the mRNA transcript using one of the DNA strands (the template strand).
Elongation
During the elongation phase, RNA polymerase moves along the DNA template strand, continuously unwinding the DNA ahead of it and rewinding it behind.
As it progresses, it synthesizes the mRNA transcript in a 5' to 3' direction by adding ribonucleotides complementary to the DNA template. In eukaryotes, RNA polymerase II is responsible for transcribing most protein-coding genes.
Termination
Transcription termination differs between prokaryotes and eukaryotes (polyadenylation signal). Eukaryotic mRNA also undergoes a process known as splicing, which involves intron removal and exon joining, 5' capping, and 3' polyadenylation. These cellular processes are crucial for mRNA stability, transport, and translation in eukaryotic cells.
How are Proteins Made? - Transcription and Translation Explained #66
Translation: From mRNA to Protein
Translation is the cellular mechanism by which the genetic information encoded in mRNA is decoded and used to synthesize proteins. This intricate process proceeds through three main stages: initiation, elongation, and termination.
Initiation
Translation initiation involves the assembly of the ribosome, mRNA, and the initiator tRNA (carrying methionine). In prokaryotes, the small ribosomal subunit binds to the mRNA at the Shine-Dalgarno sequence, which is located upstream of the start codon.
In eukaryotes, the small ribosomal subunit binds to the 5' cap of the mRNA and scans for the start codon (AUG). The initiator tRNA then binds to the start codon, and the large ribosomal subunit joins the complex, forming the functional ribosome.
Elongation
During elongation, the ribosome reads mRNA codons, adds corresponding amino acids to the growing polypeptide chain via tRNA, and translocates, repeating until a stop codon is reached.
Termination
Translation termination occurs when the ribosome encounters a stop codon (UAA, UAG, or UGA) in the mRNA. There are no tRNAs that recognize stop codons. Instead, release factors bind to the stop codon, triggering the release of the polypeptide chain from the ribosome. The ribosome then disassembles into its two subunits.
Protein Synthesis in Prokaryotes vs. Eukaryotes: What’s the Difference?
The Role of Proteins in Cellular Function
Proteins execute diverse cellular functions crucial for life. Structural proteins, like collagen and actin, provide mechanical support and maintain tissue architecture.1,2
Enzymes are protein catalysts that accelerate metabolic reactions, enabling efficient biochemical transformations.3 Cell signaling relies heavily on proteins functioning as receptors, ligands, and intracellular messengers, orchestrating communication pathways.
Transcription factors (TFs) play a complex role in gene expression and guide chromatin and transcription, influencing various aspects of development, disease, and variation.4 These diverse functions underscore the importance of protein synthesis and regulation for cellular homeostasis and organismal survival.
Errors in Protein Synthesis and Their Consequences
Errors in protein synthesis arising from mutations or other cellular dysfunctions can have profound consequences for cellular function and organismal health. Mutations altering the DNA sequence can lead to the production of non-functional or misfolded proteins, disrupting crucial biological processes.
Protein misfolding, for instance, can lead to the formation of toxic aggregates, including soluble oligomers and fibrillar amyloid deposits, which are linked with neurodegeneration in Alzheimer's and Parkinson's disease.5
These protein synthesis defects can manifest in a variety of ways, depending on the affected protein and its role in the cell. The latest advances in genetic therapies, including gene editing-based therapeutics, offer promising avenues for correcting protein synthesis errors and treating associated diseases.6
Conclusion
Protein synthesis is fundamental to all life. Understanding the molecular mechanisms of protein synthesis is crucial not only for comprehending fundamental biological processes but also for advancing medicine.
This knowledge is essential for developing novel therapeutics targeting a wide range of diseases, from cancer and infectious diseases to genetic disorders and neurodegenerative conditions, ultimately paving the way for more effective diagnostic and treatment strategies.
References
- Yang, W., Meyers, M., & Ritchie, R. (2019). Structural architectures with toughening mechanisms in Nature: A review of the materials science of Type-I collagenous materials. Progress in Materials Science. https://doi.org/10.1016/J.PMATSCI.2019.01.002.
- Miyoshi, H., & Adachi, T. (2014). Topography design concept of a tissue engineering scaffold for controlling cell function and fate through actin cytoskeletal modulation. Tissue engineering. Part B, Reviews, 20 6, 609-27. https://doi.org/10.1089/ten.TEB.2013.0728.
- Williams, M. (2005). Enzyme Assays. Current Protocols in Pharmacology, 28. https://doi.org/10.1002/0471141755.ph0300s28.
- Lambert, S., Jolma, A., Campitelli, L., Das, P., Yin, Y., Albu, M., Chen, X., Taipale, J., Hughes, T., & Weirauch, M. (2018). The Human Transcription Factors. Cell, 172, 650-665. https://doi.org/10.1016/j.cell.2018.01.029.
- Chiang, A., Kastrup, C., & Vogan, J. (2017). Protein Misfolding Diseases. Annual review of biochemistry, 86, 21-26. https://doi.org/10.1146/annurev-biochem-061516-044518.
- Vaschetto, L. M. (2022). CRISPR/Cas and Gene Therapy: An Overview. In CRISPR-/Cas9 Based Genome Editing for Treating Genetic Disorders and Diseases, 85-89. ISBN 9780367542863. CRC Press (Taylor & Francis Group). Boca Raton, FL, USA.
Further Reading