RNA and Genetic Code PDF

## RNA ### Chapter VIII: Genetic Expression - determines the structure and function of living organisms - produces specific anatomical and physiological characteristics that distinguish one organism from another - follows the genetic information stored in the genetic material received from its p...

## RNA ### Chapter VIII: Genetic Expression - determines the structure and function of living organisms - produces specific anatomical and physiological characteristics that distinguish one organism from another - follows the genetic information stored in the genetic material received from its parents - the end product of genetic expression is protein synthesis ### Genes - control the synthesis of specific polypeptide chains which constitute the precursors of proteins - a polypeptide chain is a long chain of amino acids linked together by peptide linkage; its synthesis requires the transfer of genetic info from the gene to the cytoplasm where the polypeptide chain is synthesized ### Genetic Expression - The transfer of information from the DNA to protein. - During the initial stage of gene expression, genetic information stored in DNA is transferred to RNA ### Transcription: RNA Synthesis - The process by which RNA molecules are synthesized on a DNA template. - The ribonucleotides sequence of RNA written in the genetic code is then capable of directing the process of translation - During translation, polypeptide chains are synthesized ### RNA polymerase - directs the synthesis of the three types of RNA (messenger, ribosomal and transfer RNA) that are complementary to DNA templates. - RNA polymerase has the same requirements as DNA polymerase except it uses ribonucleotide triphosphates rather than the deoxy forms - n(NTP) + DNA ➡️ Mg++ (NMP)n + RNA + n(PPi) - n(NTP): a certain number of ribonucleoside triphosphates - Enzyme: RNA polymerase - DNA: DNA Template - (NMP): a sequence with the same number of ribonucleoside monophosphates - n(ppi): number of diphosphate groups released ### The Holoenzyme - The holoenzyme from E. coli has been shown to consist of subunits called (a, B, B' and σ). - The sigma 'σ' subunit can be removed from the complex without loss of catalytic activity to the remaining core enzyme - The sigma component is believed to play a regulatory function and to be involved in recognition of promoters (the points along the DNA template where RNA transcription is initiated) ### Synthesis of RNA - The process of transcription occurs on a DNA template that constitutes a gene. #### A Structural Gene - defined as a sequence of nucleotides which specifies the amino acid sequence (i.e the structure) of a polypeptide chain and its transcript is called, after processing, a messenger RNA - The gene that is transcribed but not translated (tRNA and rRNA) ### Chapter VII: The Genetic Code - The gene or unit factor has been accepted since early Mendelian genetics as the functional units of genetics. - The recognition of the gene as a store of genetic information in a chemical language spelled out in a unique sequence of deoxyribonucleotides has led to what Crick called the **Central Dogma of molecular genetics.** - This concept entails that the flow of information in biological systems progresses mainly from **DNA to RNA and from RNA to proteins.** - Many studies have been directed toward clarifying the way by which genes perform their functions and how a mutation might cause a phenotypic change. - It has become clear that the linear sequence of the four types of deoxyribonucleotides along the gene which may contain hundreds or even thousands of these units, specify the linear sequence of amino acids in a polypeptide chain #### The genetic code - Any disruption or change in the sequence of only one or more nucleotides may lead to change in the polypeptide, which may be so severe as to endanger the life of the the organism itself - the genetic information in DNA is first transferred to a complementary RNA through transcription. - The complementary ribonucleotides in the messenger RNA (mRNA) must direct the linear insertion of amino acids into a polypeptide chain during translation on the ribosome. - The fundamental question would be: how an RNA molecule consisting of only four types of nucleotides (A, U, C and G) can specify 20 amino acids? - Active research was carried out to answer this question, which led to the discovery of the **Genetic Code.** - This is the language in which genetic information is stored. - In this chapter, we shall deal with the nature of the genetic code and it's general properties. ### I. Nature of the Genetic Code: - The earlier theoretical postulates about the nature of the genetic code were subjected to experimentation which proved that: - The genetic code is triplet in nature: Code words, or codons, each consisting of three ribonucleotides direct the insertion of a single amino acid into a polypeptide chain during its synthesis. - The genetic code is nonoverlapping: i.e. each triplet code is translated independently of its neighbours. - The genetic code is comma free: i.e. each codon in the mRNA is not separated from the neighbouring codons by any nucleotides serving as commas or punctuation signals. - There are codons which code for initiation of the polypeptide chain as well as for its termination. - The genetic code is unambiguous: i.e. any triplet cannot specify except one animo acid - The genetic code is degenerate: i.e. there is more than one codon assigned for each amino acid. - The genetic code is universal: i.e. the code applies equally to viruses, bacteria and eukaryotes ### 2. The Code Dictionary - Taken together, the various techniques taken to decipher the genetic code have yielded a dictionary of 61 triplet codon: amino acid assignments. - The remaining three triplets are termination signals, not specifying any amino acids. - The table below designates the assignments in an illustrative form, first suggested by Crick for code dictionary | First Position | Second Position | Third Position | |---|---|---| | U | U | Phe | | U | C | Phe | | U | A | Leu | | U | G | Leu | | C | U | Leu | | C | C | Leu | | C | A | Leu | | C | G | Leu | | A | U | Ileu | | A | C | Ileu | | A | A | Ileu | | A | G | Met | | G | U | Val | | G | C | Val | | G | A | Val | | G | G | Val | | U | U | Ser | | U | C | Ser | | U | A | Ser | | U | G | Ser | | C | U | Pro | | C | C | Pro | | C | A | Pro | | C | G | Thr | | A | U | Thr | | A | C | Thr | | A | A | Thr | | A | G | Asn | | G | U | Ala | | G | C | Ala | | G | A | Ala | | G | G | Ala | | U | U | Tyr | | U | C | Tyr | | U | A | STOP | | U | G | STOP | | C | U | His | | C | C | His | | C | A | Gln | | C | G | Gln | | A | U | Asn | | A | C | Asn | | A | A | Lys | | A | G | Lys | | G | U | Asp | | G | C | Asp | | G | A | Glu | | G | G | Glu | | U | U | Cys | | U | C | Cys | | U | A | STOP | | U | G | Trp | | C | U | Arg | | C | C | Arg | | C | A | Arg | | C | G | Arg | | A | U | Ser | | A | C | Ser | | A | A | Arg | | A | G | Arg | | G | U | Gly | | G | C | Gly | | G | A | Gly | | G | G | Gly | ### Further properties of the genetic code are given below #### Degeneracy and Wobble - The degenerate nature of the code is immediately apparent when we inspect the code dictionary. - While tryptophan and methionine are encoded by only single triplets, most amino acids are specified by two, three or four triplets. - Three amino acids (serine, arginine and leucine) are coded by six triplets each - Degeneracy shows a certain pattern. Most often, in a set of codes specifying the same amino acids, The first two letters are the same, with only the third differing. - This led to what Crick called Wobble hypothesis. He proposed that during translation, the first two positions of each codon must be very precise. The third position, however, is often less specific. - The wobble would allow the anticodon of a single tRNA type to pair with more than one triplet in mRNA, often without changing the amino acid. U at the first position of the tRNA anticodon may pair with A or G at the third position of mRNA triplet. - Also, G may likewise pair with U or C. - Inosine, one of the peculiar bases found in tRNA may pair with C, U or A. - Thus, a tRNA molecule of specific anticodon sequence can bind to more than one codon ### b. Initiation and Termination Codons - Initiation of protein synthesis in vivo is highly specific. - The initial amino acid inserted into all polypeptide chains in bacteria is N-formyl methionine (fmet), while it is methionine in eukaryotes - Only one codon codes for methionine, i.e. AUG, and this is sometimes called the initial codon. - Three other triplets, UAA, UAG and UGA serve as termination codons. - They are not recognized by tRNA molecules, and termination of translation occurs when they are encountered. ### c. Universality of the Genetic Code - It has become evident through extensive research from 1960 to 1978 that the genetic code is universal, applying equally to viruses, bacteria and eukaryotes. - The nature of mRNA and the translation machinery seemed to be very similar in these organisms. - For example, cell-free systems derived from bacteria could translate eukaryotic mRNAs. - Many recent studies involving recombinant DNA technology have revealed that eukaryotic genes can be inserted into bacteria and transcribed and translated - Certain exceptions, however, to the coding dictionary were discovered in the case of transcribed mitochondrial DNA. - This type of DNA, however, is extrachromosomal, and is related to extrachromosomal inheritance.