How your cell makes very important proteins - Part 4

Mutations in other body cells only cause trouble when they cause cancer or related diseases. Mutagens are chemical or physical agents that interact with DNA to cause mutations. Physical agents include high-energy radiation like X-rays and ultraviolet light. Chemical mutagens fall into several categories. Chemicals that are base analogues that may be substituted into DNA, but they pair incorrectly during DNA replication. Interference with DNA replication by inserting into DNA and distorting the double helix. Chemical changes in bases that change their pairing properties. Tests are often used as a preliminary screen of chemicals to identify those that may cause cancer. Most carcinogens are mutagenic and most mutagens are carcinogenic. Scientists have recognized a number of tumor viruses that cause cancer in various animals, including humans. About 15% of human cancers are caused by viral infections that disrupt normal control of cell division. All tumor viruses transform cells into cancer cells through the integration of viral nucleic acid into host cell DNA. Point mutations involve alterations in the structure or location of a single gene. Generally, only one or a few base pairs are involved. Point mutations can signficantly affect protein structure and function. Point mutations may be caused by physical damage to the DNA from radiation or chemicals, or may occur spontaneously. Point mutations are often caused by mutagens. The change of a single nucleotide in the DNA’s template strand leads to the production of an abnormal protein. Point mutations within a gene can be divided into two general categories. Base-pair substitutions - is the replacement of one nucleotide and its partner with another pair of nucleotides. Base-pair insertions or deletions - are additions or losses of nucleotide pairs in a gene.

How your cell makes very important proteins - Part 3

Universal: in all living organisms. A codon in messenger RNA is either translated into an amino acid or serves as a translational start/stop signal. Consists of a single RNA strand that is only about 80 nucleotides long. Each carries a specific amino acid on one end and has an anticodon on the other end. A special group of enzymes pairs up the proper tRNA molecules with their corresponding amino acids. tRNA brings the amino acids to the ribosomes, 3 dimensional tRNA molecule is roughly “L” shaped. Ribosomes facilitate the specific coupling of tRNA anticodons with mRNA codons during protein synthesis. The 2 ribosomal subunits are constructed of proteins and RNA molecules named ribosomal RNA or rRNA. The ribosome has three binding sites for tRNA. The P site, The A site, The E site. A specific enzyme called an aminoacyl-tRNA synthetase joins each amino acid to the correct tRNA. We can divide translation into three stages
• Initiation
• Elongation
• Termination
The AUG start codon is recognized by methionyl-tRNA or Met. Once the start codon has been identified, the ribosome incorporates amino acids into a polypeptide chain. RNA is decoded by tRNA (transfer RNA) molecules, which each transport specific amino acids to the growing chain. Translation ends when a stop codon (UAA, UAG, UGA) is reached. The initiation stage of translation brings together mRNA, tRNA bearing the first amino acid of the polypeptide, and two subunits of a ribosome. In the elongation stage, amino acids are added one by one to the preceding amino acid. The final step in translation is termination. When the ribosome reaches a STOP codon, there is no corresponding transfer RNA. Instead, a small protein called a “release factor” attaches to the stop codon. The release factor causes the whole complex to fall apart: messenger RNA, the two ribosome subunits, the new polypeptide. The messenger RNA can be translated many times, to produce many protein copies. mRNA binds to a ribosome, and the transfer RNA corresponding to the START codon binds to this complex. Ribosomes are composed of 2 subunits (large and small), which come together when the messenger RNA attaches during the initiation process. Elongation: the ribosome moves down the messenger RNA, adding new amino acids to the growing polypeptide chain. The ribosome has 2 sites for binding transfer RNA. The first RNA with its attached amino acid binds to the first site, and then the transfer RNA corresponding to the second codon bind to the second site. The ribosome then removes the amino acid from the first transfer RNA and attaches it to the second amino acid. At this point, the first transfer RNA is empty: no attached amino acid, and the second transfer RNA has a chain of 2 amino acids attached to it. The elongation cycle repeats as the ribosome moves down the messenger RNA, translating it one codon and one amino acid at a time. The process repeats until a STOP codon is reached. A number of ribosomes can translate a single mRNA molecule simultaneously forming a polyribosome.

Polyribosomes enable a cell to make many copies of a polypeptide very quickly. In a eukaryotic cell. The nuclear envelope separates transcription from translation. Extensive RNA processing occurs in the nucleus
Prokaryotic cells lack a nuclear envelope, allowing translation to begin while transcription progresses. The new polypeptide is now floating loose in the cytoplasm if translated by a free ribosome. Polypeptides fold spontaneously into their active configuration, and they spontaneously join with other polypeptides to form the final proteins. Often translation is not sufficient to make a functional protein, polypeptide chains are modified after translation. Sometimes other molecules are also attached to the polypeptides: sugars, lipids, phosphates, etc. All of these have special purposes for protein function. Completed proteins are targeted to specific sites in the cell. Two populations of ribosomes are evident in cells: free ribsomes (in the cytosol) and bound ribosomes (attached to the ER). Free ribosomes mostly synthesize proteins that function in the cytosol. Bound ribosomes make proteins of the endomembrane system and proteins that are secreted from the cell. Ribosomes are identical and can switch from free to bound. Polypeptide synthesis always begins in the cytosol. Synthesis finishes in the cytosol unless the polypeptide signals the ribosome to attach to the ER. Polypeptides destined for the ER or for secretion are marked by a signal peptide. A signal-recognition particle (SRP) binds to the signal peptide. The SRP brings the signal peptide and its ribosome to the ER. The natural replication of DNA produces occasional errors. DNA polymerase has an editing mechanism that decreases the rate, but it still exists. Typically genes incur base substitutions about once in every 10,000 to 1,000,000 cells. Since we have about 6 billion bases of DNA in each cell, virtually every cell in your body contains several mutations. Mutations can be harmful, lethal, helpful, silent. However, most mutations are neutral: have no effect. Only mutations in cells that become sperm or eggs—are passed on to future generations.

To be continued........

How your cell makes very important proteins - part 2

The original transcript from the DNA is called pre-mRNA. It contains transcripts of both introns and exons. The introns are removed by a process called splicing to produce messenger RNA (mRNA). Ribozymes are catalytic RNA molecules that function as enzymes and can splice RNA. RNA splicing removes introns and joins exons. RNA Splicing can also be carried out by spliceosomes. How is it possible that there are millions of human antibodies when there are only about 30,000 genes? Alternative splicing refers to the different ways the exons of a gene may be combined, producing different forms of proteins within the same gene-coding region. Alternative pre-mRNA splicing is an important mechanism for regulating gene expression in higher eukaryotes. Proteins often have a modular architecture consisting of discrete structural and functional regions called domains. In many cases different exons code for the different domains in a protein. Translation is the RNA-directed synthesis of a polypeptide. Translation involves :mRNA. Ribosomes - Ribosomal RNA. Transfer RNA, Genetic coding – codons. Genetic information is encoded as a sequence of nonoverlapping base triplets, or codons. The gene determines the sequence of bases along the length of an mRNA molecule. Codons: 3 base code for the production of a specific amino acid, sequence of three of the four different nucleotides. Since there are 4 bases and 3 positions in each codon, there are 4 x 4 x 4 = 64 possible codons. 64 codons but only 20 amino acids, therefore most have more than 1 codon. 3 of the 64 codons are used as STOP signals; they are found at the end of every gene and mark the end of the protein. One codon is used as a START signal: it is at the start of every protein.

To be continued.........