Proteins: From Genes to Degradation

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.