10.11
Proteins: From Genes to Degradation
Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. Th…
Cells have to follow a multi-layered process to synthesize an accurately folded protein from the information encoded in the genes.
This process has two major steps, transcription and translation.
Transcription is the transfer of information from DNA to a messenger RNA or mRNA molecule.
Here, the RNA polymerase II copies the information encoded in the DNA of a gene into a messenger or pre-mRNA. The nucleotide sequence of the DNA defines the genetic code of the mRNA.
The pre-mRNA then needs to undergo a series of elaborate processing steps, such as 5’ capping, 3’ polyadenylation, and splicing in the nucleus to form a mature mRNA.
After an initial quality check in the nucleus, the mature mRNA is then transported through nuclear pore complexes to the cytoplasm.
In the cytoplasm, the ribosome performs a quality check on the mRNA, and the incorrectly processed mRNAs are degraded.
During translation, the ribosome translates the correctly processed mRNA into a chain of amino acids with the help of tRNAs.
The amino acid sequence in a polypeptide is dependent on the triplet codons in the mRNA.
The newly formed polypeptide chain is then folded into a protein with the help of chaperones. This leads to the functional tertiary structure of the protein.
An error in the translation process may result in a wrong polypeptide chain and, hence, a misfolded protein that can be toxic to the cell.
Such misfolded or abnormal proteins are rapidly tagged with ubiquitin molecules and degraded in the proteasomes.
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Q1: What is the role of the ribosome in translating mRNA into protein?
The ribosome is the cellular machine that reads mRNA codons and catalyzes peptide bond formation between amino acids. It contains the peptidyl transferase center, which catalyzes the formation of peptide bonds during protein synthesis. The ribosome moves along the mRNA, ensuring each codon is matched with the correct amino acid to build the growing protein chain.
Q2: How does translation begin at the start codon?
Translation begins when initiation factors recognize the start codon (AUG) on the mRNA and position the ribosome correctly. The small ribosomal subunit binds to the mRNA, and initiation factors help deliver the first tRNA carrying methionine. Once the large ribosomal subunit joins, the ribosome is ready to begin elongation and protein synthesis.
Q3: What is the function of tRNA in protein synthesis?
Transfer RNA (tRNA) molecules deliver amino acids to the ribosome during translation. Each tRNA is activated by aminoacyl tRNA synthetases, which attach the correct amino acid to the tRNA. The tRNA recognizes the mRNA codon through its anticodon, ensuring the right amino acid is added to the growing protein chain.
Q4: How does translation end and what happens to the completed protein?
Translation terminates when the ribosome encounters a stop codon (UAA, UAG, or UGA). Release factors recognize the stop codon and trigger the release of the completed polypeptide chain from the ribosome. The newly synthesized protein then undergoes folding, often with assistance from molecular chaperones and protein folding mechanisms.
Q5: What happens to proteins after they are synthesized?
After synthesis, proteins fold into their functional three-dimensional structures with help from molecular chaperones. Proteins may then be modified, transported to specific cellular locations, or marked for degradation. Damaged or unnecessary proteins are targeted for regulated and targeted protein degradation through cellular quality control mechanisms.
Q6: How does the cell ensure translation accuracy?
The cell maintains translation accuracy through multiple checkpoints during protein synthesis. Aminoacyl tRNA synthetases verify correct amino acid-tRNA pairing before delivery to the ribosome. The ribosome's peptidyl transferase center also discriminates between correct and incorrect tRNAs, minimizing errors in the growing protein chain.
Q7: What quality control mechanisms remove defective proteins?
Cells use the ubiquitin proteasome pathway to identify and degrade defective proteins. Ubiquitin tags mark proteins for destruction, and the proteasome recognizes these tags and breaks down the protein. This system removes misfolded proteins and regulates protein levels to maintain cellular health and function.