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DNA and RNA are the molecular forms of genetic information. The structure of every protein and every biomolecule are the results of information passed on from the nucleotide sequence of nucleic acids. Information for the structure of a polypeptide chain is stored in a polynucleotide chain of DNA. Sequence of bases in a particular segment of DNA will determine the sequence of amino acids in a polypeptide chain. Information from DNA is transferred to RNA and from RNA to protein synthesizing machinery (Central Dogma). (Lewin, 1985)
Thus, the nucleic acids have complex and diverse structures that make them ideally suited for the various functions that have to be carried out.
Double helix structure of DNA
DNA is formed by two antiparallel polynucleotide chains, which are coiled in a helical structure around a central axis. The antiparallel strands give rise to a right-handed double helix. The backbones, which are formed by alternating deoxyribose and phosphate group, face the outside of the double helix towards the aqueous environment forming the hydrophilic part of the DNA. The side chain consisting of purine and pyrimidine bases are enclosed inside forming the hydrophilic region of the double helix
The bases of each structure are almost planar and perpendicular to the axis of double helix. A base of one strand pairs with the base of other strand, which are in the same plane according to the complementarity (adenine and thymine, cytosine and guanine). Two H-bond are formed between adenine and thymine and three between guanine and cytosine.(this is the reason for the difficulty in separation the two strands). Stability of the double helix is due to
H-bonds between the bases
Vander Waals interactions between the stacked bases. The bases on the interior are stacked upon the other like the stacking of coins.
The double helix makes a complete turn every 34 A, has a diameter of about 20A. The distance between two nucleotides is 3.4 A, hence there are 10 nucleotides per complete turn. Each base pair is rotated 360 around the axis relative to the next base pair. The double helix has a narrow grove of diameter of 12A and a wide groove with a diameter of 22A. (Source: Weil, 1996)
Fig. Watson - Crick Model for the structure of double helix DNA
(Source: Kratz, 2009)
Structure of RNA
RNA is formed of single stranded polypeptide chain, which consists of a phosphorylated pentose as the backbone and bases as side chains, which are either purine or pyrimidine. The bases are adenine, guanine, cytosine, and uracil. The polynucleotide chain runs from 5' carbon to 3' carbon. The nucleotides are connected by phosphodiester bond between 5' carbon and 3' carbon of the sugar. The bases are linked to the 1' carbon of the sugar by N-glycosidic linkage. The sugar is a ribose (OH at the 2 carbon of the pentose). (Source: Alberts etal, 2008)
Fig: A: primary structure of RNA. B: secondary structure of RNA.
(Source: RNA structure, n.d)
Similarities in structure between DNA and RNA.
The primary structure of DNA and RNA are almost same because both are having their monomers as nucleotides, which give rise to polynucleotide chains.
DNA has several hundred millions of nucleotides. RNA has fewer with only tens to thousands of nucleotides. A nucleotide consist of
A phosphate group attached to 5'carbon of sugar
A base attached to the 1'C of the sugar through N-glycosidic linkage
The backbone of the polynucleotide chain is formed by alternating units of sugar and phosphate group. Two sugars are linked together by phosphodiester linkage. The bases are attached as side chains to 1'Carbon through N-glycosidic linkage. In DNA the sugar is a deoxyribose whereas in RNA, the sugar is a ribose.
In nucleic acids, the bases attached to the 1' Carbon of the sugar is of five types. They are adenine and guanine collectively called purine and cytosine, thymine and uracil collectively called pyrimidine. Purines are formed of double ring and the pyrimidines are formed of single ring.
(Source: Lodish et al, 2004)
Fig. the nitrogenous bases
(Source: Kratz, 2009)
Adenine, guanine and cytosine are found in both DNA and RNA. Thymine is found only in DNA and uracil is found only in RNA. The 5' terminal of polynucleotide chain has a hydroxyl or phosphate group while the 3' end ends up at hydroxyl group on the 3' Carbon of the end sugar.
Fig. polynucleotide chain of DNA and RNA
(Source: Polynucleotide chain of DNA and RNA, n.d)
Functions of DNA
Using the parental double strand, daughter strands are produced. The parental strands are separated (semi conservative) or not separated (conservative) and then used as template for synthesis of daughter strands.
Sometimes the base sequence can change and undergo mutation according to change in the environment in order to be compatible to that changed environment.
Since the strands are complementary to each other daughter strands formed are also complementary to parent strands and hence there is less chance of misinterpreting the information.
Due to the hydrogen bonds between the bases and base stacking, the double helix is very difficult to separate. Unlike RNA, DNA has no OH at 2'carbon of the sugar, which makes it less liable to hydrolysis at normal temperature. Thymine that has a methyl group protects the DNA from denaturing enzymes. (Source: Sharma, N.B, 2010)
Presence of thymine makes DNA neutral due to presence of methyl group. Thymine also repairs DNA by deamination of cytosine to uracil. (Source: Becker et al, 2006)
Functions of RNA
Due to the presence of OH group at 2' carbon of the sugar in RNA, it is more likely to be unstable. The OH group makes it more reactive. If exposed to alkaline solution, RNA can be broken down into mononucleotides. Due to this reason, RNA can perform many specific functions in the cell.
RNA is single stranded unlike DNA, which is double stranded. Single stranded nature enables flexibility to base pair within itself between different regions and fold into many secondary structures like hairpins, stem loops and pseudo knots to carry its diverse functions. (Source: Lodish et al, 2004)
Presence of uracil makes RNA very reactive due to the absence of methyl group in uracil and this enables RNA to carry out diverse functions in protein synthesis.
(Source: Becker etal, 2006)
Some RNAs are catalytic in function and are called ribozymes. Ribozymes catalyze a process called splicing where there is cutting and removal of the introns and ligation of exons. Some RNAs can undergo self splicing. (Source: Nelson and Cox, 2003)
Three types of RNA
RNA is of three types.
t RNA (Structure and function)
In transfer RNA the sequence of bases forms the primary structure. tRNA comprises of about 40 to 90 nucleotides and weigh around 30000. The secondary structure of tRNA is called "cloverleaf". The cloverleaf conformation is maintained by small regions, which are complementary. The cloverleaf has four arms that are named according to their structure and functions. They are:
The acceptor arm: Present at the top and here the bases are paired but CCA at the 3` end are unpaired and exceeds beyond 5` end.
D arm(dihydrouracil loop): Present at the left side and named so due to the presence of modified uracil base dihydrouridine.
T Ïˆ C arm: Present at the right side and is named so due to the presence of these three sequences. (Source: Nelson and Cox, 2000)
Anticodon arm: Present at the bottom and is named for the presence of anticodon at its tip.
Extra arm or variable loop: Present between the T Ïˆ C arm and the anticodon.
(Source: Lewin, 1985)
According to Weaver in 2002, the cloverleaf simply explains the base pairing pattern. The true three-dimensional structure is inverted L.
Fig: The cloverleaf structure
Fig: The cloverleaf structure
(Source: The cloverleaf, n.d)
The main function of tRNA is base pairing. The tRNA with the help of enzyme amino acyl tRNA synthetase carries only specific amino acids, which correspond to it. At the base of cloverleaf, the codon present is anticodon, which reads the codon of mRNA. This is catalyzed by amino acyl t RNA synthetase. Thus, amino acids are incorporated into right proteins.
(Source: Weaver, 2002)
The acceptor arms covalently bonds to particular amino acids and this is called charging. It is regulated by enzyme amino acyl t RNA synthetase.
(Source: Weaver, 2002)
3. mRNA (structure and function)
The size of mRNA is very much variable because the proteins translated by mRNAs are of different sizes. A polycistromic mRNA can be 3 times longer than the largest ribosomal RNA since it can have about 104 nucleotides. It can be about 120 times longer than a tRNA and weigh 3.5x106. Monocistronic mRNA length is unlimited to the coding region between the initiation codon (AUG) and the termination codon (UAG, UAA or UGA).
On the 5'side that is on the initiation codon site, there is the leader region and on the 3' side, which is on the termination codon side, there is the tail region. There are also intercistronic C region of variable length.
At 5'cap 7 methylalanylate is connected to the terminal nucleate of the RNA by 5'-5'
triphosphate linkage which protects the mRNA from enzymatic degradation. At the 3' end of mRNA, poly (A) tail is present.
The eukaryotic mRNA retains 5' and 3' untranslated regions (UTRs). 5' UTR can be hundreds of nucleotides in length and 3'UTR can be kilo base in length. In prokaryotes, 5' and 3' UTRs are shorter than that of eukaryotes.
(Source: Weil, 1996)
Fig: Structure of mRNA.
(Source: mRNA structure, n.d)
The genetic information is transcribed from DNA into mRNA in the form of triplet code. Each amino acid is encoded by one or more than three codons in mRNA. There are start codons and stop codons. Translation starts from the start codon which codes for methonine and the codon is AUG. Translation proceeds from 5' to 3' terminus of mRNA and stops when reaching the stop codons (UAA, UGA, UAG). The undisturbed sequence of codons in mRNA, called a reading frame is translated into sequence of amino acids in a polypeptide chain.
(Source: Alberts et al, 2008).
r RNA (structure and function)
In prokaryotes, there are three types of rRNAs. These are 5S, 16S and 23S where as in eukaryotes, there are four types of r RNAs and these are 5S, 5.8S, 18S and 28S. It represents about 70- 80% of total cellular RNA. rRNA is a single stranded polypeptide chain which forms a helical structure. It is highly folded, compact and 3dimensional structure that forms the major component of a ribosome.
rRNA forms the primary structure of a ribosome.
It forms catalytic region of the ribosome for peptide bond formation in tRNA with amino acids. It binds tRNA and other accessory proteins for protein synthesis.
Figure: Structure of rRNA.
(Source: structure of rRNA, n.d)
Fig: The Mechanism of Protein Synthesis (Central Dogma).
(Source: Protein synthesis mechanism, n.d)