CHAPTER 21: Unit 8. DNA Leads to RNA and Protein

DNA or otherwise called deoxyribonucleic acid is the building block of the life. It contains the information the cell requires to synthesize protein and to replicate itself, to be short it is the storage repository for the information that is required for any cell to function. Watson-Crick has discovered the current-structure of DNA in 1953.The famous double-helix structure of DNA has its own significance. There are basically four nucleotide bases, which make up the DNA. Adenine (A), Guanine (G), Thymine (T) and Cytosine(C). A DNA sequence looks some thing like this “ATTGCTGAAGGTGCGG”. DNA is measured according to the number of base pairs it consists of, usually in kBp or mBp(Kilo/Mega base pairs). Each base has its complementary base, which means in the double helical structure of DNA, A will have T as its complimentary and similarly G will have C.  nbsp; DNA molecules are incredibly long. If all the DNA bases of the human genome were typed as A, C, T and G, the 3 billion letters would fill 4,000 books of 500 pages each! The DNA is broken down into bits and is tightly wound into coils, which are called chromosomes; human beings have 23 pairs of chromosomes. These chromosomes are further broken down into smaller pieces of code called Genes. The 23 pairs of chromosomes consist of about 70,000 genes and every gene has its own function. As I have mentioned earlier, DNA is made up of four nucleotide bases, finding out the arrangement of the bases is called DNA sequencing, there are various methods for sequencing a DNA, it is usually carried out by a machine or by running the DNA sample over a gel otherwise called gel electrophoresis. A typical sequence would look like this “ATTTGCTGACCTG”.

Fig Sample genetic code with complementary strands.

Determining the gene’s functionality and position of the gene in the chromosome is called gene mapping. Recent developments show that scientists are mapping every gene in the human body. They named their project Human Genome Project (HGP), which involves careful study of all the 70,000 genes in human body. Whew! That’s some thing unimaginable. When there is a change in the genetic code it is called mutation. The significance of a DNA is very high. The gene’s sequence is like language that instructs cell to manufacture a particular protein. An intermediate language, encoded in the sequence of Ribonucleic Acid (RNA), translates a gene’s message into a protein’s amino acid sequence. It is the protein that determines the trait. This is called central dogma of life.

Figure: Central dogma of life.

Notes: Genes are DNA sequences instruct cells to produce particular proteins, which in turn determine traits. Chromosomes are strings of genes. Mutations are changes in gene’s DNA sequence.RNA is somewhat similar to DNA; they both are nucleic acids of nitrogen-containing bases joined by sugar-phosphate backbone. How ever structural and functional differences distinguish RNA from DNA. Structurally, RNA is a single-stranded where as DNA is double stranded. DNA has Thymine, where as RNA has Uracil. RNA nucleotides include sugar ribose, rather than the Deoxyribose that is part of DNA. Functionally, DNA maintains the protein-encoding information, whereas RNA uses the information to enable the cell to synthesize the particular protein.

RNADNASingle-StrandedDouble-StrandedHas Uracil as a baseHas Thymine as a baseRibose as the sugarDeoxyribose as the sugarUses protein-encoding informationMaintains protein-encoding informationTable above: Differences between DNA and RNA

Notes: DNA stores the genetic information, where as RNA uses the information to help the cell produces the protein.

Transcription, TranslationTranscription is a process of making an RNA strand from a DNA template, and the RNA molecule that is made is called transcript. In the synthesis of proteins, there are actually three types of RNA that participate and play different roles:Messenger RNA(mRNA), which carries the genetic information from DNA and is used as a template for protein synthesis.Ribosomal RNA(rRNA), which is a major constituent of the cellular particles called ribosomes on which protein synthesis actually takes place.A set of transfer RNA(tRNA) molecules, each of which incorporates a particular amino acid subunit into the growing protein when it recognizes a specific group of three adjacent bases in the mRNA.DNA maintains genetic information in the nucleus. RNA takes that information into the cytoplasm, where the cell uses it to construct specific proteins, RNA synthesis is transcription; protein synthesis is translation.RNA differs from DNA in that it is single stranded, contains Uracil instead of Thymine and ribose instead of deoxyribose, and has different functions. The central dogma depicts RNA as a messenger between gene and protein but does not adequately describe RNA’s other function.Transcription is highly controlled and complex. In Prokaryotes, genes are expressed as required, and in multicellular organisms, specialized cell types express subsets of gene. Transcription factors recognize sequences near a gene and bind sequentially, creating a binding transcription. Transcription proceeds as RNAP inserts complementary RNA bases opposite the coding strand of DNA. Antisense RNA blocks gene expression.Messenger RNA transmits information in a gene to cellular structures that build proteins. Each three mRNA bases in a row forms a codon that specifies a particular amino acid. Ribosomal RNA and proteins form ribosomes, which physically support the other participants in protein synthesis and help catalyze formation of bonds betweens amino acids.In eukaryotes, RNA is often altered before it is active. Messenger RNA gains a cap of modified nucleotides and a poly A tail. Introns are transcribed and cut out, and exons are reattached by ribozymes. RNA editing introduced bases changes that alter the protein product in different cell types.The genetic code is triplet, non-overlapping, continuous, universal, and degenerate. As translation begins, mRNA, tRNA with bound amino acids, ribosomes, energy molecules and protein factos assemble. The mRNA leader sequence binds to rRNA in the small subunit of a ribosome, and the first codon attracts a tRNA bearing methionine. Next, as the chain elongates, the large ribosomal subunit attaches and the appropriate anticodon parts of tRNA molecules form peptide bonds, a polypeptide grows. At a stop codon, protein synthesis ceases. Protein folding begins as translation proceeds, with enzymes and chaperone proteins assisting the amino acid chain in assuming its final functional form. Translation is efficient and economical, as RNA, ribosomes, enzymes, and key proteins are recycled.A much-detailed explanation could be found in the book ‘Molecular Biology’ by David Freifelder. I suggest you read this book if you interested in detailed knowledge about transcription and translation.

Reference: https://www.goodreads.com/en/book/show/3990923-molecular-biology

Reference:
https://www.youtube.com/watch?v=gG7uCskUOrA

Protein synthesis is one of the most fundamental biological processes by which individual cells build their specific proteins. Within the process are involved both DNA (deoxyribonucleic acid) and different in their function ribonucleic acids (RNA). The process is initiated in the cell’s nucleus, where specific enzymes unwind the needed section of DNA, which makes the DNA in this region accessible and a RNA copy can be made. This RNA molecule then moves from the nucleus to the cell cytoplasm, where the actual the process of protein synthesis take place.Proteins are synthesized stepwise by the polymerization of amino acids in a unidirectional manner, beginning at the N-terminus and ending at the C-terminus. The amino acids are linked by the formation of peptide bonds, and the resulting polypeptide chain contains one of 20 different amino acids at each position.

Reference: https://commons.wikimedia.org/wiki/File:Difference_DNA_RNA-EN.svg

All cells function through their proteins. Protein function is defined by their molecular function, localization within cell and involvement in a particular biological process. All components of protein function are defined by the exact composition, structure and conformation of the proteins, which is encrypted within the DNA region (called locus) encoding that protein. With the process of protein synthesis biological cells generate new proteins, which on the other hand is balanced by the loss of cellular proteins via degradation or export.Transcription is the first of overall two protein synthesis steps. During transcription, the information encoded in the DNA is copied to a RNA molecule as one strand of the DNA double helix is used as a template. The RNA molecule is sent to the cytoplasm, which helps to bring all components required for the actual protein synthesis together – amino acids, transport RNAs, ribosomes, etc. In the cytoplasm the protein polymers are actually “synthesized” through chemical reactions – that is why the process is known as “protein synthesis” or even more precisely – “protein biosynthesis”. The RNA copy of the protein genetic information encoded in DNA molecule is produced in the nucleus and it is called messenger RNA (mRNA). Each mRNA encodes the information for a single protein and is much smaller in size compared to the DNA molecule. This makes possible for mRNA molecules to exit the nucleus through tiny openings called nuclear pores. Once it exits the nucleus and enters the cytoplasm, the mRNA could interact with a cellular structure known as a ribosome, which serves as the cell’s assembler within the process of protein synthesis. The ribosome consists of proteins and ribosome RNA molecules (rRNA), which are organized in two subunits. The mRNA initially binds to just one of the ribosome sub-units.When the mRNA interacts with the big ribosome sub-unit, this triggers the approach of another RNA molecule, called transfer RNA (tRNA). The tRNA molecule possess a specific sequence of 3-bases (anti-codon), which hast to complement a corresponding sequence (codon) within the mRNA sequence. When it finds it, it attaches to the mRNA, as the other end of the tRNA is “loaded” with an amino acid. At this point arrives the other sub-unit of the ribosome and a complete structure is formed. The first tRNA binds to a so called “start codon”, which is one and the same for all proteins. As the complete ribosome structure is formed, another tRNA molecule approaches. The next tRNA differ from the first one and is carrying another amino acid. Again, the tRNA must have an anti-codon that matches complementary the second codon of the mRNA. The two amino acids carried by the first two tRNAs are bind together with help from the ribosome and using cellular energy in the form of adenosine triphosphate (ATP).The above steps repeat until there are uncoupled codon sequences on the mRNA – thus the chain of amino acids grows longer. Once the sequence of amino acids is successfully assembled in a protein, the two ribosome sub-units separate from each other, to be joined again for later use.The actual sequence of amino acids forms the so-called primary structure of the proteins. Depending on the exact composition and order of the amino acids in the protein sequence, the chain folds into a three-dimensional shape. When this happens, the protein is complete.The process of protein synthesis takes place in multiple ribosomes simultaneous and all throughout the cell cytoplasm. A living cell can synthesize hundreds of different proteins every single second.

Reference: https://www.proteinsynthesis.org/what-is-protein-synthesis/