The Information in DNA Determines Cellular Function via Translation

A schematic shows a ribosome attached to a single horizontal strand of MRNA. Inside the ribosome, two molecules of TRNA have bound to complementary sequences on the MRNA. Amino acids are attached to the TRNA molecules, forming a peptide chain.

The ribosome assembles the polypeptide chain

To manufacture protein molecules, a cell must first transfer information from DNA to mRNA through the process of transcription. Then, a process called translation uses this mRNA as a template for protein assembly. In fact, this flow of information from DNA to RNA and finally to protein is considered the central dogma of genetics, and it is the starting point for understanding the function of the genetic information in DNA.

But just how does translation work? In other words, how does the cell read and interpret the information that is stored in DNA and carried in mRNA? The answer to this question lies in a series of complex mechanisms, most of which are associated with the cellular structure known as the ribosome. In order to understand these mechanisms, however, it's first necessary to take a closer look at the concept known as the genetic code.

What is the genetic code?

More on translation

At its heart, the genetic code is the set of "rules" that a cell uses to interpret the nucleotide sequence within a molecule of mRNA. This sequence is broken into a series of three-nucleotide units known as codons (Figure 1). The three-letter nature of codons means that the four nucleotides found in mRNA — A, U, G, and C — can produce a total of 64 different combinations. Of these 64 codons, 61 represent amino acids, and the remaining three represent stop signals, which trigger the end of protein synthesis. Because there are only 20 different amino acids but 64 possible codons, most amino acids are indicated by more than one codon. (Note, however, that each codon represents only one amino acid or stop codon.) This phenomenon is known as redundancy or degeneracy, and it is important to the genetic code because it minimizes the harmful effects that incorrectly placed nucleotides can have on protein synthesis. Yet another factor that helps mitigate these potentially damaging effects is the fact that there is no overlap in the genetic code. This means that the three nucleotides within a particular codon are a part of that codon only — thus, they are not included in either of the adjacent codons.

A schematic shows a horizontal row of 15 nucleotides above a row of four amino acids and a stop signal. The nucleotides, which are represented by green, yellow, blue, or orange rectangles, are joined end to end by ribose sugars, which are represented by grey horizontal cylinders. The row of 15 nucleotides can be divided into five groups of three from left to right. Each of the three-nucleotide units, or codons, corresponds to an amino acid or stop signal in the row below it.

Figure 1: In mRNA, three-nucleotide units called codons dictate a particular amino acid. For example, AUG codes for the amino acid methionine (beige).

Figure Detail

The idea of codons was first proposed by Francis Crick and his colleagues in 1961. During that same year, Marshall Nirenberg and Heinrich Matthaei began deciphering the genetic code, and they determined that the codon UUU specifically represented the amino acid phenylalanine. Following this discovery, Nirenberg, Philip Leder, and Har Gobind Khorana eventually identified the rest of the genetic code and fully described which codons corresponded to which amino acids.

Reading the genetic code

Redundancy in the genetic code means that most amino acids are specified by more than one mRNA codon. For example, the amino acid phenylalanine (Phe) is specified by the codons UUU and UUC, and the amino acid leucine (Leu) is specified by the codons CUU, CUC, CUA, and CUG. Methionine is specified by the codon AUG, which is also known as the start codon. Consequently, methionine is the first amino acid to dock in the ribosome during the synthesis of proteins. Tryptophan is unique because it is the only amino acid specified by a single codon. The remaining 19 amino acids are specified by between two and six codons each. The codons UAA, UAG, and UGA are the stop codons that signal the termination of translation. Figure 2 shows the 64 codon combinations and the amino acids or stop signals they specify.

A table lists 64 different combinations of the nucleotides uracil (U), cytosine (C), adenine (A), and guanine (G) when they are arranged in three-nucleotide-long codons. The four possible identities of the first nucleotide in the codon are listed in a column on the left side of the table. The same four possible identities of the second nucleotide in the codon are listed in a row along the top of the table. The four possible identities of the third nucleotide in the codon are listed in a column on the right side of the table. The inside of the table is divided into a four by four grid. Each box in the grid contains all the codons that may result when combining the corresponding 1st, 2nd, and 3rd position nucleotides listed in the left column, top row, and right column, respectively. Colored spheres representing amino acids appear in the table beside the three-nucleotide codons that code for them.

Figure 2: The amino acids specified by each mRNA codon. Multiple codons can code for the same amino acid.

Figure Detail

What role do ribosomes play in translation?

As previously mentioned, ribosomes are the specialized cellular structures in which translation takes place. This means that ribosomes are the sites at which the genetic code is actually read by a cell. Ribosomes are themselves composed of a complex of proteins and specialized RNA molecules called ribosomal RNA (rRNA).

A schematic shows a TRNA molecule that contains an anticodon nucleotide sequence at the bottom. At the top, a single amino acid is bound to the amino acid attachment site at one end of the TRNA molecule.

Figure 3: A tRNA molecule combines an anticodon sequence with an amino acid.

Figure Detail

During translation, ribosomes move along an mRNA strand, and with the help of proteins called initiation factors, elongation factors, and release factors, they assemble the sequence of amino acids indicated by the mRNA, thereby forming a protein. In order for this assembly to occur, however, the ribosomes must be surrounded by small but critical molecules called transfer RNA (tRNA). Each tRNA molecule consists of two distinct ends, one of which binds to a specific amino acid, and the other which binds to a specific codon in the mRNA sequence because it carries a series of nucleotides called an anticodon (Figure 3). In this way, tRNA functions as an adapter between the genetic message and the protein product. (The exact role of tRNA is explained in more depth in the following sections.)

What are the steps in translation?

Like transcription, translation can also be broken into three distinct phases: initiation, elongation, and termination. All three phases of translation involve the ribosome, which directs the translation process. Multiple ribosomes can translate a single mRNA molecule at the same time, but all of these ribosomes must begin at the first codon and move along the mRNA strand one codon at a time until reaching the stop codon. This group of ribosomes, also known as a polysome, allows for the simultaneous production of multiple strings of amino acids, called polypeptides, from one mRNA. When released, these polypeptides may be complete or, as is often the case, they may require further processing to become mature proteins.

Initiation

A schematic shows a ribosome attached to one end of a single horizontal strand of MRNA. Inside the ribosome, the three leftmost terminal nucleotides are a bright red color, marking the start codon.

Figure 4: During initiation, the ribosome (grey globe) docks onto the mRNA at a position near the start codon (red).

Figure Detail

At the start of the initiation phase of translation, the ribosome attaches to the mRNA strand and finds the beginning of the genetic message, called the start codon (Figure 4). This codon is almost always AUG, which corresponds to the amino acid methionine. Next, the specific tRNA molecule that carries methionine recognizes this codon and binds to it (Figure 5). At this point, the initiation phase of translation is complete.

A schematic shows a ribosome attached to the left end of a single horizontal strand of MRNA. Inside the ribosome, a TRNA molecule has attached to the first three nucleotides in the MRNA sequence. An amino acid is attached to the top of the TRNA molecule.

Figure 5: To complete the initiation phase, the tRNA molecule that carries methionine recognizes the start codon and binds to it.

Figure Detail

Elongation

A schematic shows a ribosome attached to one end of a single horizontal strand of MRNA. Three TRNA molecules are present inside the ribosome. The first TRNA molecule has attached its amino acid to the growing peptide chain and is leaving the ribosome. The second and third TRNA molecules have attached to the MRNA sequence by their anticodon sequences. Two amino acids are bound to the top of the second TRNA molecule, and one amino acid is bound to the top of the third TRNA molecule.

Figure 6: Within the ribosome, multiple tRNA molecules bind to the mRNA strand in the appropriate sequence.

Figure Detail

A schematic shows a ribosome attached to the middle of a single horizontal strand of MRNA. Inside the ribosome, two TRNA molecules are attached by their anticodon sequences to complementary sequences on the MRNA stranad. The first TRNA molecule has a growing chain of five amino acids attached to the top. The second TRNA molecule has a single amino acid attached to the top.

Figure 7: Each successive tRNA leaves behind an amino acid that links in sequence. The resulting chain of amino acids emerges from the top of the ribosome.

Figure Detail

The next step in translation, called elongation, begins when the ribosome shifts to the next codon on the mRNA. At this point, the corresponding tRNA binds to this codon and, for a short time, there are two tRNA molecules on the mRNA strand. The amino acids carried by these tRNA molecules are then bound together. After this binding has occurred, the ribosome shifts again, and the first tRNA, which is no longer connected to its corresponding amino acid, is released (Figure 6). Now, the third codon in the mRNA strand is ready to bind with the appropriate tRNA (Figure 7). Once again, the tRNA binds to the mRNA strand, the third amino acid is added to the series, the ribosome shifts, and the second tRNA (which no longer carries an amino acid) is released. This process is repeated along the entire length of the mRNA, thereby elongating the polypeptide chain that is emerging from the top of the ribosome (Figure 8).

A schematic shows a top-down view of a ribosome attached to the right end of a single horizontal strand of MRNA. Inside the ribosome, a TRNA molecule is attached to the MRNA sequence via its anticodon sequence. A long chain of amino acids is attached to the top of the TRNA molecule and protrudes from the top of the ribosome.

Figure 8: The polypeptide elongates as the process of tRNA docking and amino acid attachment is repeated.

Figure Detail

Termination

Eventually, after elongation has proceeded for some time, the ribosome comes to a stop codon, which signals the end of the genetic message. As a result, the ribosome detaches from the mRNA and releases the amino acid chain. This marks the final phase of translation, which is called termination (Figure 9).

A schematic shows the disassembling of the MRNA-ribosome-TRNA-protein complex at the end of translation. Each component of the translation complex is separated and suspended in the cytoplasm of the cell.

Figure 9: The translation process terminates after a stop codon signals the ribosome to fall off the RNA.

Figure Detail

What happens after translation?

For many proteins, translation is only the first step in their life cycle. Moderate to extensive post-translational modification is sometimes required before a protein is complete. For example, some polypeptide chains require the addition of other molecules before they are considered "finished" proteins. Still other polypeptides must have specific sections removed through a process called proteolysis. Often, this involves the excision of the first amino acid in the chain (usually methionine, as this is the particular amino acid indicated by the start codon).

Once a protein is complete, it has a job to perform. Some proteins are enzymes that catalyze biochemical reactions. Other proteins play roles in DNA replication and transcription. Yet other proteins provide structural support for the cell, create channels through the cell membrane, or carry out one of many other important cellular support functions.