Nucleic acids are the most important constituents of the living cells. They are comprised DNA and RNA (deoxyribonucleic acid and ribonucleic acid respectively). DNA and RNA are polymeric chains where covalent bonds connect each monomer units. Structures of the monomer in DNA and RNA are shown below.
Fig. 1 Structures of monomers in DNA & RNA.
Each monomer units has 5-carbon sugar (2' deoxyribose in DNA and ribose in RNA). The bases are differentiated from 5-carbon sugar by designating the carbon atoms by primes (1', 2', 3' â€¦) in 5-carbon sugar. A phosphate residue connects successive monomer units to the 3' hydroxyl of one unit to the hydroxyl of one unit to hydroxyl on 5' carbon and so on forming phosphodiester linkage between two successive sugar residues resulting in the formation of long chain of DNA and RNA. The phosphate groups are negatively charged having pka of about 1. The backbone of DNA and RNA has phosphodiester-linked sugar residues.
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Each monomer contains heterocyclic bases; purine and pyrimidine. Adenine (A) and Guanine (G) are purine having double nitrogenous ringed structure, Cytosine (C) and Thymine (T) in DNA/ Uracil (U) in RNA are pyrimidine having single nitrogenous ringed structure.
Mathews et al, 1999
DNA is the carrier of genetic information which can be pass on to next generations. DNA also have an ability to undergo mutations. Mutations are the main cause to bring about evolutions.
Since DNA is double stranded it cannot directly enter into protein synthesis, an intermediatory called RNA is produced dy DNA to aid in protein synthesis.
Fig2: Structures of base.
STRUCTURE OF DNA and RNAs
Fig 3: Structure of DNA.
DNA is double-stranded helix formed by pairing of Adenine with Thymine, And Guanine with Cytosine which run in opposite direction (antiparallel).The DNA has two terminal ends; 5' hydroxyl or phosphate terminal and 3' hydroxyl or phosphate terminal showing charged polarity.
(Source: Murray R.K etal, 1988)
According to Chargaff, the concentration of deoxyadenosine (A) nucleotides equals to that of Thymidine (T) nucleotides (A=T) whereas the concentration of deoxyguanosine (G) nucleotides equals to deoxycytidine (C) nucleotides (G= C). The double strands are formed by the hydrogen bonds between the bases of purine and pyrimidine of the successive linear molecules, the van der Waals forces and the hydrophilic phosphate deoxyribose backbone that are in contact with outside environment shields the hydrophobic bases which stack on one another perpendicular to vertical axis of helical allowing DNA to be in double stranded form and chemically stable.This form contributes in genetic information that be pass to next generations.
Double hydrogen bond is formed by base pairing of Adenine (A)-Thymine (T) and triple hydrogen bond is formed by Guanine-Cytosine. The bond formed by Guanine and Cytosine is stronger than bond formed by Adenine and Thymine.
Thymine is methylated form of base and is extremely neutral in acidic condition, hence it protect DNA from DNAases and any other enzymes.
Mathews,C.K, et al,1999
Deciphering the Genetic Code (n,d.)
Fig4: Double stranded DNA.
Right handed helices of DNA are commonly found and bases form the spiral in clockwise direction when viewed from the top. One complete turn, that is, 360 degree of helix has 10 base pairs and every one base pair is at 36 degree. The surface of the double helix contains two grooves: major groove and minor groove. The major groove is more direct to bases and minor groove faces the sugar backbone. Harlt,D.L et al, 2001
RNA (ribonucleic acid)
RNA constitutes one of the nucleic acid components which occur primarily as single stranded. Instead of long loose chain as that of DNA, the RNA form different structures. The differences in their structures permit them to perform specific functions in cells.
The backbone of RNA is formed by polar and hydrophilic sugar phosphate linkage as that of DNA. The sugar is ribose (where as deoxyribose in case of DNA due to the absence of OH group), which is the 2' carbon has hydroxyl group. Instead of Thymine as in DNA, Uracil is present which can base pair with Adenine. The purine (Adenine and Guanine) and pyrimidine (Cytosine and Uracil) are present in RNA as well. The presence of more number of water molecules forms hydrogen bonds to the 2-OH group of RNA, which makes RNA more rigid than DNA.
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Base pairing between complementary sequences within the RNA (intramolecular) give rise to stem-loop structures or it may give rise to more complex structure when the loops interact with each other where as base pairing in DNA occurs between two different strands to form double helix.
By the process of DNA transcription, the RNA is produced in the presence of enzyme called RNApolymerase which can further translate for the process of protein synthesis. For the synthesis of proteins, three types of RNA are required. They are:
Voet D et al, 2006
mRNA (messenger RNA)
Source: Return to The Medical Biochemistry Page (n.d.)
Fig 5: Structure of mRNA.
Messenger RNA has start codon called AUG which initiates the translation of amino acids. The first amino acid that binds to start codon is methionine, and then followed by Leucine. Three stop codons- UAA, UGA and UAG of tRNA do not bind with the amino acids,thus further binding of amino acids to tRNA are inhibited because no mRNA recognize these codons, thus, with the help of certain proteins and factors called release factors, termination of polypeptide chains occur.
1-methtylguanosine triphoshate or cap at 5'terminal of mRNA that link to an adjacent 2'-O-methyribonucleoside at its 5'-hydroxyl through three phosphates. 6-methyladenylates and other 2'-O-ribose methylated nucleotides are frequently found internal of mRNA molecules.
At the 3'-hydroxyl terminal of mRNA has an attached polymer of adenylate residues containing 20-250 nucleotides in length. This is called poly (A) tail.
(Source: Hartl,D.L etal, 1986)
2) STRUCTURE OF tRNA
Source: RNA-Ribonucleic Acids(n.d.)
Fig 6: Structure of tRNA.
Transfer RNA molecules are smaller in size ranging from about 70 to 90 nucleotides than mRNA and are single stranded nucleic acid. The tRNA molecules are formed from larger primary transcript, hence it has 5'-monophosphate terminus and 3'-OH terminus.
The primary structures (that is, nucleotide sequence) of tRNA fold extensively intrastrand complementarity occur to form the secondary structures which look like a cloverleaf in two dimensions and this form of structures are not observed in mRNA.
The tRNA (cloverleaf) contain four loops or stems; DHU loop, TÏˆC loop, variable loop and anticodon.From side view, the TÏˆC loop and DHU loop are approximately near to each other. The other region or loop consist of three nucleotides (anticodons) that base pair with codons of mRNA and at 3'-hyroxyl terminus attaches the amino acids.
(Source: Hartl D.L, et al, 2001
3) STRUCTURE OF rRNA (ribosomal RNA)
The ribosome present in cytoplasm acts as machines in the production of protein from mRNA templates.
The rRNA is the largest among the other RNAs.
The ribosome present in mammals has a sedimentation velocity of 80S (Svedberg units). It contains two subunits; larger subunit and smaller subunit. The larger subunit, that is, 60S contains 5SrRNA, 5.8S rRNA and 28SrRNA; and more than 50specific polypeptides are present.
The smaller subunits, that is, 40S contain 18S rRNA and about 30 specific polypeptides are present. 5S Ribosomal RNA is transcript independently and the rest are processed from single 45Sprecursor RNA molecules present in nucleolus.
These subunits are not present in other RNAs.
The ribosomal RNAs are highly methylated and are packed in nucleolus with the specific protein.
In prokaryotes, the smaller 30S and 50S associate to form 70S particles.
Murray,R.K, e tal, 1988
UNUSUAL STRUCTURE OF DNA
A peculiar form of DNA having left handed helix called Z-DNA has been discovered by Alexander Rich in 1979.
Syn and Anti are most stable orientations when bases are attached to the deoxyribose sings. Example is given below.
The purine and pyrimidine are always oriented in syn and anti respectively due to the alternating purine and pyrimidine in each strands found in polynucleotides in Z-DNA, hence, the orientation of bases will alternate resulting in zigzag pattern of the phosphates.
(Source: Hartl D.L, 2001)
FUNCTIONS OF DNA
DNA is the carrier of genetic information in all cells and in many viruses. When DNA replicates, each strand of DNA acts as a template for assembling its complimentary strand. Now each daughter DNA will have one parental strand and one daughter strand. This is also semi-conservatives of DNA and in this way the characters of parents are transmitted to the off springs.
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DNA has an ability to undergo mutation to bring about evolution. It is basically the changes occur in the sequence of bases in DNA.
Mutations are of various types: deletion or insertion, inversion or replacement of bases, transitions (purine is replaced by purine and pyrimidine is replaced by pyrimidine), and transversion (purine is replaced by pyrimidine and pyrimidine is replaced by purine). These mutations can be good, bad or be different. Lodish et al, 1986
DNA contains the coded information for the protein synthesis that is basic building block. The proteins are synthesized by the process of transcriptions and translations.
Simple-sequence DNA is short, tandemly repeated sequences that are found in cetromeres and parts of chromosomes as well. Simple-sequence DNA often called as satellite. The bands are formed at different positions other than main band and these bands are called satellite bands. These are mainly concentrated at specific location in chromosomes. Microsatellites are the repeats containing 1-13 base pairs originated from "backward slippage" of template strand of daughter strand during DNA replication. Depending on its occurrence in genes, at least 14 different types of neuromuscular diseases are caused and some of them are Myotonic dystrophy and spinocerebellar ataxia.
Lodish et al, 1986
FUNCTIONS OF mRNA
The genetic information carried by mRNA from DNA is used as a template for the synthesis of polypeptide because mRNA is in the form, that of long single stranded chain that contains codons. Nucleotides present in mRNA molecules, infact code for amino acids. The sets of three nucleotide sequences are read in mRNA by particular amino acids.
The presence of cap helps to protect the mRNA from attack by RNAases at 5'-hydroxyl terminal.
The function of poly (A) tail is not clearly understood but it is believed that it prevents the mRNA from attack by 3'-exonucleases and maintaining the intercellular stability.
(Source: Waver etal, 1999)
FUNCTIONS OF tRNA
Particular tRNA carries the specific amino acids to the mRNA, for example, tRNA carrying methionine is denoted as tRNAmet and serine carrying tRNA is denoted as tRNAser.
The tRNA carrying amino acids attaches to the ribosome according to the specific sequence for the synthesis of polypeptide chains.
Source: Deciphering the Genetic Code (n.d.)
Fig 9: Function of tRNA
FUNCTIONS OF rRNA
-By producing the catalytic regions in ribosomes, it provides the structure and shape.
-By interacting between the tRNA and protein machinery, it helps to speed up or catalyses protein synthesis.
Lodish,H et al, 1986
How does the structure of each particular nucleic acid make it ideally suited for its function?
DNA- DNA is double stranded formed by base pairing of two polynucleotides; the hydrophobic bases are shielded by polar hydrophilic sugar phosphate where base pairing between adenine with thymine and guanine with cytosine take place resulting in conservation of genetic information. The hydrogen bonds formed between guanine and cytosine (triple bond) is stronger than bond formed between adenine and thymine (double bond) because triple bond need more energy than double bond to break, thus hydrogen bonds formed between bases makes DNA chemically stronger. The presence of methylated Thymine protects DNA from attack by enzymes.
RNA-mRNA: since start and stop codons are present, it can initiate translation as well as terminate the synthesized proteins. Also the presence of 'cap' and 'poly (A) tail' protect the mRNA so that it can bind with tRNA to synthesize protein.
-tRNA: Presence of anticodon in one of the stems can bind with codons of mRNA so that amino acids carried by tRNA can transfer to mRNA.
-rRNA: Until both subunits do not bind to mRNA, translation will not occur. Translation will not complete if ribosomal RNA is absent.