Protein Synthesis


The idea that DNA makes RNA and RNA makes protein is sometimes referred to as the central dogma of molecular biology; the term was coined by Francis Crick, one of the co-discoverers of DNA's structure.

1. From DNA to RNA: How does the information in the DNA molecule get turned into the proteins that give our bodies structure? We won't go into this in great detail but, to give a big picture overview, here's what happens: DNA, which is a double stranded molecule, unzips down the center through the action of an enzyme called RNA polymerase. An RNA template is laid down on top of one of the DNA strands, making a near mirror image (instead of Thymine, RNA uses Uracil) of the DNA code, as shown in the table below. This template is laid down in the 5' to 3' direction. (Remember that the strands are anti-parallel.) The RNA strand is now called messenger RNA, or mRNA, and leaves the nucleus of the cell. This process of converting DNA information into RNA information is called transcription.

Whenever the DNA had this nucleotide base... the RNA will have this nucleotide base
Cytosine (C) Guanine (G)
Guanine (G) Cytosine (C)
Adenine (A) Uracil (U)
Thymine (T) Adenine (A)

2. From RNA to Amino Acid: The mRNA arrives at a ribosome. Each three letter snippet of RNA is called a codon. The RNA codons are read by the ribosome. Each codon calls for the synthesis of a particular amino acid. There are about 20 biologically important amino acids. Read the table below from left to right to look up the amino acid that is called for by each codon. For example, if the RNA codon reads "CAG," the amino acid that will be synthesized is Glutamine. If the RNA codon reads "ACG," the amino acid that will be synthesized is Threonine. (Note that, in some cases, there is more than one codon that will result in the same amino acid.) As the ribosome moves across the mRNA strand, reading the 3-letter codons, a special transport molecule called transfer RNA (tRNA) is dipatched to pick up the amino acid specified by the codon. The tRNA delivers the correct amino acid back to the ribosome, lands on the mRNA codon (the tRNA molecule has a corresponding anti-codon), and releases its amino acid cargo, where it is attached to a growing peptide chain. This process of converting RNA information into amino acids is called translation.

peptide synthesis
Note: We now know that while 80% of the human genome is transcribed, only 1% codes for proteins. If so, what is the rest of the transcribed RNA doing? We know that while every cell contains a full and complete copy of the individual's DNA, the same DNA sequences are not expressed in every cell. Heart cells are different from liver cells, which are different from brain cells and kidney cells. We believe that RNA is involved in the regulation of DNA expression. If the RNA determines which DNA sequences get expressed, and sets the timing and duration of the gene expression, then that could help to explain why every kind of cell performs a specific job despite all of them containing a full DNA sequence. Research on stem cells, which are capable of differentiating into any kind of cell in the body, holds great promise for future cures to a variety of genetic conditions including cancer.

nonpolar polar basic acidic (stop codon)
 
1st
base		 2nd base 3rd
base
U C A G
U UUU (Phe/F) Phenylalanine UCU (Ser/S) Serine UAU (Tyr/Y) Tyrosine UGU (Cys/C) Cysteine U
UUC UCC UAC UGC C
UUA (Leu/L) Leucine UCA UAA Stop (Ochre) UGA Stop (Opal) A
UUG UCG UAG Stop (Amber) UGG (Trp/W) Tryptophan     G
C CUU CCU (Pro/P) Proline CAU (His/H) Histidine CGU (Arg/R) Arginine U
CUC CCC CAC CGC C
CUA CCA CAA (Gln/Q) Glutamine CGA A
CUG CCG CAG CGG G
A AUU (Ile/I) Isoleucine ACU (Thr/T) Threonine         AAU (Asn/N) Asparagine AGU (Ser/S) Serine U
AUC ACC AAC AGC C
AUA ACA AAA (Lys/K) Lysine AGA (Arg/R) Arginine A
AUG (Met/M) Methionine ACG AAG AGG G
G GUU (Val/V) Valine GCU (Ala/A) Alanine GAU (Asp/D) Aspartic acid GGU (Gly/G) Glycine U
GUC GCC GAC GGC C
GUA GCA GAA (Glu/E) Glutamic acid GGA A
GUG GCG GAG GGG G

3. From Amino Acid to Protein: After each new amino acid comes off the assembly line, it is joined to the end of the growing peptide chain. Remember that while the base unit of each amino acid is identical, the attached R group is what gives each amino acid its unique physical properties. A good way to imagine this is to think of a chain composed of beads of different types.

Here's an animation that shows you how the whole process works.

3-D structure: Imagine that each chain of amino acids, the peptide, is like a long piece of yarn. The "primary structure" of a protein is the makeup of the strands themselves. The "secondary structure" of a protein is the way in which these strands are woven together, as strands of hair are woven together into a braid, or as fibers are interlaced into a sheet of fabric. The "tertiary structure" of a protein is the way in which those braided strands are twisted and folded to make a complex three-dimensional structure. For example, think about how yarn can be knit into a hat, sock, or mitten; each with a unique 3-D shape.

Mutation: Now that you understand how to read DNA, let's think about what happens when a mutation occurs. A mutation is a change to the DNA. Changes can happen when a copying error occurs or when the DNA is damaged by radiation or chemical toxins. When changes occur, it's usually a bad thing but, depending on the kind of change, it can be minor or very serious. Here are some possibilities: A single letter in the DNA sequence can be substituted by another. A letter (or sequence of letters) can be inserted or deleted. A sequence of letters can be inverted (cut out, flipped and re-inserted). A sequence of letters can be duplicated one or more times. Imagine that instead of the Cs, Gs, As and Ts of the DNA, we use a sentence where each word is a codon. Here's what that sentence might look like after each kind of mutation:

Original: The quick brown fox jumped over the lazy dog.

Substitution: The quick brown fog jumped over the lazy dog. (The x became a g. The sentence remains intelligible but meaning has shifted slightly. This is also sometimes called a "point mutation" because it affects only a single point on the DNA sequence.)

Insertion: The quick brown fox gjumpe dove rth elaz ydog. (A single letter g inserted after the x shifts letters to the right, changing the breaks between our word codons and making everything after the insertion nonsensical. However, we accidentally created the word "dove" which is was unintentional but does have meaning. Maybe this is a beneficial mutation?

Deletion: The quick brown foj umpedo vert hel azyd og. (After the single letter x is deleted, every letter is shifted one position to the left. The sentence makes sense up to the point of the mutation, but then becomes scrambled.)

Multi-letter deletion: The quick fox jumped over the lazy dog. (If an entire codon gets deleted, there is no shift to the left or right. The sentence remains intelligible but the meaning might change. If the deletion doesn't happen exactly at the word codon breaks however, this would end up more like the previous two examples.)

Inversion: The quick muj xof nworbped over the lazy dog. (The inverted section makes no sense but the rest of the words are unaffected.)

Duplication: The quick brown fox brown fox brown fox jumped over the lazy dog. (The duplication of brown fox makes the sentence a bit harder to figure out but, because full codons were duplicated, it remains intelligible. If the duplication happened across codons, it might be a much bigger mess.)

Translocation: The DNA fragment is cut from one chromosome and pasted to a different one.