Translation

Proteins are complex molecules composed of amino acid monomers. They are present in all life forms and perform essential functions such as providing structural support, acting as enzymes that catalyze biological reactions, and regulating metabolic signals from outside the cell. Given how abundant and important proteins are, you might ask: how are proteins made? In this article, we will discuss the protein synthesis process known as translation: what it is, how it takes place, its purpose, and what happens when errors occur.

Definition of translation in biology

In biology, translation is the second stage in gene expression and protein synthesis, as described by the central dogma. The central dogma states that genetic information flows from DNA to mRNA, then from mRNA to protein.

The mRNA template is a copy of a gene’s nucleotide sequence written into RNA during transcription. The genetic information in mRNA's nucleotide sequence is translated into protein sequences which consist of 20 various amino acids. These amino acids are represented by letters, which make up the protein alphabet.

During translation, the nucleotide sequence in mRNA is read as “words” that consist of three nucleotides, from one end of the mRNA to the other. Such three-letter words are known as codons (or triplet codons).

Amino acids have varying chemistry (e.g., acidity, polarity, etc.) and structure (helices, zigzags, and other shapes). Variations in amino acids in protein sequences result in variations in the function and structure of proteins. The amino acids in a protein sequence give the protein its unique properties. For example, while both muscle protein and hair protein have 20 amino acids, the sequences of these proteins differ.

Translation occurs in ribosomes –the structures that serve as the site of protein synthesis in the cell. When they are not performing protein synthesis, ribosomes dissociate into large and small ribosomal subunits.

• The small ribosomal subunit binds the mRNA template.

• The large ribosomal subunit binds the transfer RNAs (tRNAs).

The translation process takes place in three general steps: initiation, elongation, and termination.

First step in translation (biology): initiation

Translation starts with ribosomal assembly, leading to the formation of the initiation complex. The formation of the initiation complex is as follows:

1. The small ribosomal subunit binds to the initiator tRNA molecule (tRNAi), which contains the amino acid methionine in archaea and eukaryotes and the N-formyl-methionine in bacteria. The tRNAi is charged because it carries an amino acid.

2. The small ribosomal subunit bound to the charged tRNAi travels across the mRNA strand up to the start codon “AUG”, which signifies the beginning of translation. AUG also marks the beginning of the reading frame (the nucleotide base sequence in mRNA that encodes polypeptides).

3. The anticodon on the tRNAi binds to the start codon through base pairing. The anticodon is a codon in the tRNA that is complementary to a codon in the mRNA.

4. The small ribosomal subunit, mRNA, and charged tRNAi bind to the large ribosomal subunit. This forms the initiation complex. Proteins called initiation factors bring together these components. The cell uses energy in the form of Guanosine triphosphate (GTP) to fuel the process.

Second step in translation (biology): elongation

During elongation, the ribosome continues to translate codons and add amino acids, making the amino acid chain even longer. The ribosome consists of three compartments:

1. A (aminoacyl) site

2. P (peptidyl) site

3. E (exit) site

The A site is the binding site for tRNA, while the P site is the binding site for the polypeptide chain. The tRNAi that carries methionine binds to the P site, while the succeeding tRNA that carries aminoacyl binds to the A site by pairing the next codon in the mRNA. An elongation factor escorts aminoacyl tRNA to the ribosome.

The ribosome transfers three nucleotides along the mRNA strand, putting the next codon in the free A site. This process is called translocation as it translocates the peptidyl tRNA from the A site to the P site, while moving the dissociated tRNAi from the P site to the E site.

Third step in translation (biology): termination

Translation ends during the termination stage. Termination takes place when a nonsense or stop codon (UAA, UAG, or UGA) enters the A site. Release factors recognize these nonsense codons and signal the hydrolysis of the bond between the tRNA and the P site polypeptide chain. This releases the newly made protein, which needs to be folded to function.

The small and large ribosomal subunits then detach from each other and from the mRNA before taking part in another translation initiation complex. When ribosomes complete translation, the mRNA becomes degraded so its nucleotides can participate in another transcription reaction.

Diagram of the translation process

The process of translation is simplified and visualized in the following diagram (Fig. 2):

Purpose of translation in biology

More than any other component except for water, proteins make up most of the mass of living organisms as they perform almost every function of the cell. Translation serves the important function of synthesizing proteins from mRNA.

What happens when there are errors during translation?

Translation is the stage that is most prone to errors during protein synthesis. To illustrate, the misincorporation of amino acids during translation is estimated to take place for every 1,000 to 10,000 codons translated. This means that 15% of protein molecules at average length will have at least one misincorporated amino acid.

Such errors can lead to protein misfolding, protein aggregation (where misfolded proteins are assembled and stored), and even cell death. In fact, a wide range of neurodegenerative illnesses, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, are attributed to protein misfolding. On the other hand, multiple sclerosis and amyotrophic lateral sclerosis (ALS) are linked to amino acid misincorporation during translation as caused by mutations in the genetic code.