The human body is comprised of an enormous number of cells. Each cell has its unique shape and function. In order to carry out its many different roles, the cell relies on tiny protein machines called enzymes. The cell utilizes a "user's manual" in order to produce the right proteins in the right quantities and at the right time. This user's manual is in the form of DNA, which constitutes the hereditary database in each cell. DNA, through its genes, serves as a template for the production of proteins. The following video describes the protein biosynthesis process, starting from the transcription of its gene and progressing all the way through to protein folding and guidance into its region of activity. Notice the different steps of this process and the site where each step occurs (nucleus, cytoplasm, etc.).

 

 

 

The video was produced by the Human Genome Project. Click here for more info.

The monumental Human Genome Project lasted about 16 years (1990 – 2006) during which the human genome was deciphered to an accuracy level of 99.9%. The project is still ongoing, currently focusing on unmapped sequences in-between genes. The project was, and still is, of great significance, as it contributed much to our knowledge and understanding of molecular processes in the human body. Similar projects are focused at deciphering the genomes of several plants and animals of great scientific interest, such as monkeys, mice, wheat, rice and many more.

The process by which proteins are produced follows the rules of the central dogma of molecular biology, which constitutes the key to all the processes that take place in every cell in our body. According to the central dogma, the sequence of information transfer is described as DNA → RNA → protein. DNA, or deoxyribonucleic acid, is comprised of two long polymeric strands. The building blocks of each strand are four different nucleotides (also known as DNA bases) which are abbreviated A, C, G and T. Any combination of three sequential nucleotides (known as a codon) encodes a specific amino acid. Since amino acids are the building blocks of proteins, each protein can be described as a sequence of amino acids (much like a DNA strand can be described as a sequence of nucleotides).

The expression of a gene (a protein-encoding DNA segment) as a protein product is a two-step process – transcription followed by translation. Initially, the two DNA strands open up, allowing access for the enzyme RNA polymerase, which synthesizes an RNA molecule according to the DNA template. RNA is a slightly different type of nucleic acid than DNA, as it is comprised of only a single strand that is complementary to the DNA strand from which it was transcribed. At the end of the transcription process, the new RNA strand separates from the DNA and exits the cell nucleus through a designated pore in the nuclear membrane. The DNA returns to its original double strand form.

Once the new RNA molecule (now termed messenger RNA or mRNA) reaches the cytoplasm it attaches to a ribosome in which translation takes place. The ribosome anchors the RNA and allows tRNA molecules to bind it. The tRNA acts as a mediator between the nucleotide information presented by the mRNA and the amino acid sequence of the target protein. Each tRNA molecule contains a 3-nucleotide sequence complementary to one of the 64 possible codons. In addition, each tRNA also carries a "cargo" in the form of the amino acid specified by this codon. The ribosome catalyzes the formation of a bond between the two amino acids on adjacent tRNA molecules. The ribosome than advances along the RNA strand in order to allow access for the next tRNA molecule. This process is repeated until the amino acid sequence of the newly-formed protein is complete. At this point the ribosome detaches and the protein product is transferred to its site of activity by specialized proteins.

Proteins are 3-dimensional macromolecules. This means that formation of the amino acid sequence is not the end of the synthesis process. In order to gain functionality a protein must be folded into its 3-dimensional form. There are several different mechanisms of protein folding, from simple spontaneous folding in the cytoplasm to protein-assisted folding in the endoplasmic reticulum (ER) or in the cell membrane. The folding process is vital for transforming the protein into its most stable and functional state. Aberrant protein folding can result in loss of function or sometimes even in the formation of large protein masses that can interfere with cell function and lead to disease.

Protein biosynthesis is a very complex process. In this article I have tried to simplify it to the best of my ability. Whole textbooks have been written on the subject, so I do apologize for any inaccuracies or lacking explanations.

Erez Garty
Department of Biological Chemistry
Weizmann Institute of Science

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