9.11: Proteins: From Genes to Degradation

Proteins: From Genes to Degradation
JoVE Core
Molecular Biology
A subscription to JoVE is required to view this content.  Sign in or start your free trial.
JoVE Core Molecular Biology
Proteins: From Genes to Degradation

12,259 Views

02:11 min
November 23, 2020

Overview

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.

Transcript

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.

Key Terms and definitions​

  • Central Dogma of Molecular Biology - The flow of genetic info from DNA to RNA to protein.
  • Transcription - Synthesis of RNA from DNA, occurs in three phases.
  • Translation - The process through which mRNA is decoded to synthesize protein.
  • Protein Synthesis - The process of forming amino acids sequences by translation of mRNA.
  • Protein Degradation - The cellular process by which damaged proteins are broken down.

Learning Objectives

  • Define Central Dogma of Molecular Biology – Understand flow of genetic info (e.g., DNA to RNA to protein).
  • Contrast Transcription vs Translation – Learn two fundamental steps in central dogma (e.g., RNA synthesis vs Protein synthesis).
  • Explore Protein Synthesis – Understand how amino acid sequences are form (e.g., Translation of mRNA).
  • Explain Protein Degradation – Know how cellular process breaks down damaged proteins.
  • Apply in Context – Understand the relevance of these processes for cell function and health.

Questions that this video will help you answer

  • How does the Central Dogma of Molecular Biology define the flow of genetic information?
  • What is the difference, in terms of process and result, between transcription and translation?
  • How does protein synthesis work and what does it lead to?
  • What is protein degradation and why is it important?

This video is also useful for

  • Students – Gain knowledge about crucial biological concepts and processes.
  • Educators – Learn key terms, principles used to teach advanced biology topics.
  • Researchers – Understand essential cellular processes relevant for genetic, molecular research.
  • Science Enthusiasts – Introduce, clarify the Central Dogma of Molecular Biology.