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Overview of translation

How the nucleotide sequence of an mRNA is translated into the amino acid sequence of a polypeptide (protein).

Introduction

Take a moment to look at your hands. The bone, skin, and muscle you see are made up of cells. And each of those cells contains many millions of proteins1. As a matter of fact, proteins are key molecular "building blocks" for every organism on Earth!
How are these proteins made in a cell? For starters, the instructions for making proteins are "written" in a cell’s DNA in the form of genes. If that idea is new to you, you may want to check out the section on DNA to RNA to protein (central dogma) before getting into the nitty-gritty of building proteins.
Basically, a gene is used to build a protein in a two-step process:
  • Step 1: transcription! Here, the DNA sequence of a gene is "rewritten" in the form of RNA. In eukaryotes like you and me, the RNA is processed (and often has a few bits snipped out of it) to make the final product, called a messenger RNA or mRNA.
  • Step 2: translation! In this stage, the mRNA is "decoded" to build a protein (or a chunk/subunit of a protein) that contains a specific series of amino acids.
The central dogma of molecular biology states that information flows from DNA (genes) to mRNA through the process of transcription, and then to proteins through the process of translation.
_Image modified from "Central dogma of molecular biochemistry with enzymes," by Daniel Horspool (CC BY-SA 3.0). The modified image is licensed under a CC BY-SA 3.0 license._
In this article, we'll zoom in on translation, getting an overview of the process and the molecules that carry it out.

The genetic code

During translation, a cell “reads” the information in a messenger RNA (mRNA) and uses it to build a protein. Actually, to be a little more techical, an mRNA doesn’t always encode—provide instructions for—a whole protein. Instead, what we can confidently say is that it always encodes a polypeptide, or chain of amino acids.
Genetic code table. Each three-letter sequence of mRNA nucleotides corresponds to a specific amino acid, or to a stop codon. UGA, UAA, and UAG are stop codons. AUG is the codon for methionine, and is also the start codon.
_Image credit: "The genetic code," by OpenStax College, Biology (CC BY 3.0)._
In an mRNA, the instructions for building a polypeptide are RNA nucleotides (As, Us, Cs, and Gs) read in groups of three. These groups of three are called codons.
There are 61 codons for amino acids, and each of them is "read" to specify a certain amino acid out of the 20 commonly found in proteins. One codon, AUG, specifies the amino acid methionine and also acts as a start codon to signal the start of protein construction.
There are three more codons that do not specify amino acids. These stop codons, UAA, UAG, and UGA, tell the cell when a polypeptide is complete. All together, this collection of codon-amino acid relationships is called the genetic code, because it lets cells “decode” an mRNA into a chain of amino acids.
Each mRNA contains a series of codons (nucleotide triplets) that each specifies an amino acid. The correspondence between mRNA codons and amino acids is called the genetic code.
5' AUG - Methionine ACG - Threonine GAG - Glutamate CUU - Leucine CGG - Arginine AGC - Serine UAG - Stop 3'
Image modified from "RNA-codons-aminoacids," by Thomas Splettstoesser (CC BY-SA 4.0). The modified image is licensed under a CC BY-SA 4.0 license.

Overview of translation

How is an mRNA "read" to make a polypeptide? Two types of molecules with key roles in translation are tRNAs and ribosomes.

Transfer RNAs (tRNAs)

Transfer RNAs, or tRNAs, are molecular "bridges" that connect mRNA codons to the amino acids they encode. One end of each tRNA has a sequence of three nucleotides called an anticodon, which can bind to specific mRNA codons. The other end of the tRNA carries the amino acid specified by the codons.
There are many different types of tRNAs. Each type reads one or a few codons and brings the right amino acid matching those codons.
Ribosomes are composed of a small and large subunit and have three sites where tRNAs can bind to an mRNA (the A, P, and E sites). Each tRNA vcarries a specific amino acid and binds to an mRNA codon that is complementary to its anticodon.
Image modified from "Translation: Figure 3," by OpenStax College, Biology (CC BY 4.0).

Ribosomes

Ribosomes are the structures where polypeptides (proteins) are built. They are made up of protein and RNA (ribosomal RNA, or rRNA). Each ribosome has two subunits, a large one and a small one, which come together around an mRNA—kind of like the two halves of a hamburger bun coming together around the patty.
The ribosome provides a set of handy slots where tRNAs can find their matching codons on the mRNA template and deliver their amino acids. These slots are called the A, P, and E sites. Not only that, but the ribosome also acts as an enzyme, catalyzing the chemical reaction that links amino acids together to make a chain.
Want to learn more about the structure and function of tRNAs and ribosomes? Check out the tRNA and ribosomes article!

Steps of translation

Your cells are making new proteins every second of the day. And each of those proteins must contain the right set of amino acids, linked together in just the right order. That may sound like a challenging task, but luckily, your cells (along with those of other animals, plants, and bacteria) are up to the job.
To see how cells make proteins, let's divide translation into three stages: initiation (starting off), elongation (adding on to the protein chain), and termination (finishing up).

Getting started: Initiation

In initiation, the ribosome assembles around the mRNA to be read and the first tRNA (carrying the amino acid methionine, which matches the start codon, AUG). This setup, called the initiation complex, is needed in order for translation to get started.

Extending the chain: Elongation

Elongation is the stage where the amino acid chain gets longer. In elongation, the mRNA is read one codon at a time, and the amino acid matching each codon is added to a growing protein chain.
Each time a new codon is exposed:
  • A matching tRNA binds to the codon
  • The existing amino acid chain (polypeptide) is linked onto the amino acid of the tRNA via a chemical reaction
  • The mRNA is shifted one codon over in the ribosome, exposing a new codon for reading
    Elongation has three stages:
    1) The anticodon of an incoming tRNA pairs with the mRNA codon exposed in the A site.
    2) A peptide bond is formed between the new amino acid (in the A site) and the previously-added amino acid (in the P site), transferring the polypeptide from the P site to the A site.
    3) The ribosome moves one codon down on the mRNA. The tRNA in the A site (carrying the polypeptide) shifts to the P site. The tRNA in the P site shifts to the E site and exits the ribosome.
    Image based on similar diagram in Reece et al.2
During elongation, tRNAs move through the A, P, and E sites of the ribosome, as shown above. This process repeats many times as new codons are read and new amino acids are added to the chain.
For more details on the steps of elongation, see the stages of translation article.

Finishing up: Termination

Termination is the stage in which the finished polypeptide chain is released. It begins when a stop codon (UAG, UAA, or UGA) enters the ribosome, triggering a series of events that separate the chain from its tRNA and allow it to drift out of the ribosome.
After termination, the polypeptide may still need to fold into the right 3D shape, undergo processing (such as the removal of amino acids), get shipped to the right place in the cell, or combine with other polypeptides before it can do its job as a functional protein.

Want to join the conversation?

  • blobby green style avatar for user Gary Vickers
    You state that AUG is the start codon and also the codon for Methionine. Do all proteins made in cells start with MET?
    (38 votes)
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    • male robot hal style avatar for user ali.kara
      N-terminal initiating methionine, although being the first amino acid, is not present at N-terminus of all proteins. This is because of a process that is known as post-translational modification. There are more than a hundred post-translational modifications known, one of which is the removal of methionine from the N-terminus of a polypeptide. N-terminal methionine is removed from a polypeptide by the enzyme methionine aminopeptidase.
      (25 votes)
  • leafers seed style avatar for user naya.black
    where are the amino acids attached to the transfer RNA coming from? in the pictures it makes it seem like they just magically appear and float into the ribosome.
    (11 votes)
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  • female robot ada style avatar for user Brendan Eilola
    Hi there

    I am curious - what stops a ribosome from attaching to another location that may be misread as an AUG when it might be uAU|Guu (Tyr + Val) for instance?
    (10 votes)
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    • female robot grace style avatar for user tyersome
      Excellent question!

      Translation is quite bit more complicated that this introductory material can cover.

      The sequence of the mRNA around a potential start codon influences whether or not it will be used§. These sequences are bound by proteins that help guide the ribosome to assemble at the correct place to start translation.
      (In fact, codons other than AUG are sometimes used as start codons!)

      This is covered in a bit more detail in a later article in this tutorial:
      https://www.khanacademy.org/science/biology/gene-expression-central-dogma/translation-polypeptides/a/the-stages-of-translation

      I also encourage you to look at some of the references for that section, which will help give you more detail on this high complex process that is still being actively studied.


      §Note: The mechanisms are very different in prokaryotic and eukaryotic organisms — they can also vary between different species and even for different genes!
      (6 votes)
  • blobby green style avatar for user jenseys43
    Why is an actual gene that codes for a protein likely to be longer?
    (5 votes)
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    • leaf green style avatar for user Sarah Mati
      This is because when a gene is transcribed by RNA polymerase into pre-mRNA, it contains both coding (exon) segments and non-coding (intron) segments. After the complementary pre-mRNA strand has been synthesised, the intron segments which do not code for any part of the protein are removed from the sequence, and the remaining exon segments are spliced together via action of RNA ligase. The removal of the introns causes the mRNA strand to be shorter than it was originally, possessing less codons. However, the loss of introns ensures that the protein translation will not be interrupted by non-coding genes.
      (14 votes)
  • blobby green style avatar for user jihan21411294
    Is the tRNA made from DNA, or its a preexisting molecule?
    (4 votes)
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  • blobby green style avatar for user Elizabeth
    what is the open reading frame? how does that fit into all of this?
    (3 votes)
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    • female robot grace style avatar for user tyersome
      An open reading frame (ORF) is a series of codons that begins with a start codon (usually AUG) and ends with a stop codon. There can be no additional stop codons within that sequence.

      In genes that lack introns (e.g. most prokaryotic genes), an ORF in the DNA sequence will define the entire translated region. If splicing occurs (i.e. in genes with introns), a final processed mRNA (transcript from a protein coding gene) will have a long ORF that directs ribosomes to produce a polypeptide.

      Does that help?
      (5 votes)
  • blobby green style avatar for user Kailloo
    What happens to the mRNA after being translated? Can it be translated again?
    (3 votes)
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  • cacteye blue style avatar for user Layla
    Are there any important enzymes involved in translation? In the article it says "the ribosome also acts as an enzyme, catalyzing the chemical reaction," but is the ribosome an enzyme or does it just ACT as an enzyme? Thanks.
    (1 vote)
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    • mr pink red style avatar for user Revan Rangotis
      Well, there is one enzyme which is crucial for translation and that is "aminoacyl tRNA synthetase". This enzyme attaches an amino acid to the tRNA. There is a different version of this for every different amino acid (so 20 of these in human bodies).

      The enzyme is a "synthetase" because it creates a new structure called "aminoacyl-tRNA", which is the tRNA which has an amino acid linked to it. The word "aminoacyl" means that an amino acid is linked to something, in this case tRNA.

      This process happens BEFORE the tRNA enters the ribosome and it takes place in the cytosol. ATP is required for that reaction.

      I hope that helps ^^
      (6 votes)
  • blobby green style avatar for user sizwengwenya037
    what removes the Introns from pre-mRNA
    (3 votes)
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  • blobby green style avatar for user sukarnadotbasu
    Re: the genetic code image
    Why are there 3 codons for stopping? Why is one not enough?
    Also then why is there just 1 codon to start? (Although I know there are other start codons but AUG seems to be made out as the major one.)
    Thanks.
    (3 votes)
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