What are you going to learn?

  • What is translation and how does it work?
  • What are codons?
  • Why are ribosomes so important for translation?
  • What is tRNA and what is its function?
  • What are post-translational modifications?
  • terms: initiator tRNA; rRNA; A, P, E sites; anticodon; aminoacyl-tRNA synthetase; initiation complex; start codon; stop codon

Translation is the second step of gene expression - the process in which the information in the gene is used to synthesize a product - usually, a protein. The first step was transcription - the synthesis of RNA from DNA. Translation is the process of synthesizing a protein from the transcribed RNA (mRNA).

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translation = RNA → protein

First let's talk about all the necessary translation components and terminology to understand the process.

Codons

A codon is the sequence of three nucleotides in the mRNA molecule. One codon specifies one amino acid - for example, a CUU codon specifies leucine, GCU alanine, etc.

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codon = sequence of 3 nucleotides; specifies an amino acid (e.g., CUU → leucine)

Ribosome

A ribosome is an organelle made of small ribosomal proteins and RNA molecules called ribosomal RNAs (rRNAs). It is composed of two subunits: a large subunit and a small subunit, that fit together. A ribosome contains three sites: 1) aminoacyl (A) site, 2) peptidyl (P) site, 3) exit (E) sites. The function of these is explained in the steps of translation below.

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Ribosomes have a large and a small subunit and 3 functional sites: A site, P site, E site.

tRNA

tRNAs (transfer RNAs) are small RNA molecules that transfer amino acids to the ribosome. They have a very specific structure because they contain four short segments that are double-helical and make the molecule look like a cloverleaf. Two of these regions are especially important: 1) anticodon, three nucleotides that bind (through base-pairing) to a complementary codon in the mRNA molecule. For example, a GCC codon in the mRNA (specifying alanine) requires a complementary CGG anticodon. 2) amino-acid-accepting arm, where the amino acid gets attached to the tRNA.

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tRNAs transfer amino acids to the ribosome.
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tRNA's structure:
1) anticodon - binds to a complementary codon
2) amino-acid-accepting arm - contains the attached amino acid

The attachment of the amino acid to the tRNA depends on enzymes called aminoacyl-tRNA synthetases. There is a different synthetase enzyme for each amino acid. Each synthetase recognizes a particular amino acid as well as all the tRNAs that accept that amino acid.

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Aminoacyl-tRNA synthetases attach an amino acid to the tRNA.

The Major Steps of Translation

After the mRNA molecule is synthesized during transcription, it travels to the cytoplasm. Here, several components bind to the mRNA: 1) the small ribosomal subunit, 2) initiation factors, 3) the so-called initiator tRNA. Initiator tRNA is a special tRNA that always carries the amino acid methionine and is required to initiate translation. These form the initiation complex that binds to the cap at the 5'-end of the mRNA. This initiation complex then moves along the mRNA to find the AUG codon specifying methionine so that the initiator tRNA can bind to it. For that reason, the AUG codon is called the start codon. Once found, tRNA pairs with the codon, the initiation factors are released and the large ribosomal subunit joins the small one.

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Translation initiation:
1) small ribosomal subunit + initiation factors + initiator tRNA form the initiation complex and bind to the 5'-end of mRNA
2) initiation complex finds the AUG codon and tRNA pairs with it
3) initiation factors are released and large ribosomal subunit joins the small one

With methionine as the first amino acid (although it can be removed later) in the protein chain, the mRNA is pulled through the ribosome in the 5'-to-3' direction and its nucleotide sequence is read in groups of three (codons) and amino acids are gradually added to the polypeptide chain.

To understand the process in more detail, we need to realize that ribosomes have three special sites: 1) aminoacyl (A) site, 2) peptidyl (P) site, 3) exit (E) site, as mentioned above. First, tRNA with the amino acid enters the A site of the ribosome where it pairs with the complementary codon. The amino acid bound to the tRNA is then linked to the peptide chain in the P site. After that, the large ribosomal subunit moves forward and the tRNA that was in the P site shifts to the E site, where it is ejected. In this way, a protein chain is gradually synthesized.

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Protein synthesis on the ribosome:
1) tRNA + amino acid bind to the A site
2) the amino acid is linked to the peptide chain in the P site
3) large ribosomal subunits moves forward, tRNA shifts to the E site and is ejected

Translation ends when the ribosome reaches the so-called stop codon. Stop codons - UAA, UAG, UGA - do not specify an amino acid and only give a signal to the ribosome to stop translation. Proteins known as release factors then bind to the stop codon and the completed protein chain is released together with the mRNA and the two ribosomal subunits dissociate.

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Stop codons (UAA, UAG, UGA) give a signal to the ribosome to stop translation.

Once the synthesized protein leaves the ribosome, it can be modified in different ways. These modifications are called post-translational modifications and they can include process like methylation (adding a methyl group), glycosylation, phosphorylation, etc. These modifications are often needed for the protein to become fully functional.

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Post-translational modifications modify the protein to become fully functional (e.g., methylation, glycosylation, etc.).

References:
Alberts, B. (2014). Essential Cell Biology. Garland Science.
Cooper, G. M., & Hausman, R. E. (2007). The cell: A molecular approach. ASM.
Pierce, B. A. (2019). Genetics: A Conceptual Approach (Seventh ed.). W. H. Freeman.
Snustad, D. P., & Simmons, M. J. (2012). Principles of Genetics. Wiley.