Back to chapter

10.11:

Proteins: From Genes to Degradation

JoVE Core
Cell Biology
This content is Free Access.
JoVE Core Cell Biology
Proteins: From Genes to Degradation

Languages

Share

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.

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. This is referred to as “The Central Dogma of Molecular Biology” – a term coined by Francis Crick.  Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are – transcription and translation.

Transcription is the synthesis of RNA molecules by RNA polymerase and other accessory proteins using DNA as the template. It happens in three phases – initiation, elongation, and termination and leads to premature RNA molecules that need to be further processed. While in eukaryotes, the whole transcription process happens inside the defined cell nucleus; transcription in prokaryotes occurs in the cytoplasm itself. Besides, while prokaryotes have only one type of RNA polymerase, eukaryotic cells have three types of RNA polymerase – I, II, and III to transcribe different RNA classes.

In eukaryotes, the processing of the pre-mRNA molecules into mature mRNA usually happens alongside transcription. It is also necessary for its transport into the cytoplasm, where it can be translated into the protein. The ribosomes in the cytoplasm decode the mRNA molecules the help of tRNA molecules, and synthesize a chain of amino acids. It is within the ribosomes that peptide bonds are formed between the amino acids leading to a polypeptide. This polypeptide is later folded into an active protein that can perform its functions inside the cell.

Any defects in this entire process can turn out to be detrimental to the cell. Therefore, cells enforce quality checks at various stages to ensure the synthesis of the right protein. Any defective RNA or protein molecule synthesized is hence degraded through pre-defined mechanisms.

Suggested Reading

  1. Clancy, S. & Brown, W. (2008) Translation: DNA to mRNA to Protein. Nature Education 1(1):101