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BIOMOLECULES
NUCLEIC ACIDS
Nucleic acids, and DNA in particular, are key macromolecules for the continuity of life. DNA bears the hereditary information that’s passed on from parents to children, providing instructions for how (and when) to make the many proteins needed to build and maintain functioning cells, tissues, and organisms. How DNA carries this information, and how it is put into action by cells and organisms, is complex, fascinating, and fairly mind-blowing, and we’ll explore it in more detail in the section on molecular biology. Here, we’ll just take a quick look at nucleic acids from the macromolecule perspective.
Roles of DNA and RNA in cells
Nucleic acids , macromolecules made out of units called nucleotides, come in two naturally occurring varieties: deoxyribonucleic acid ( DNA ) and ribonucleic acid ( RNA ). DNA is the genetic material found in living organisms, all the way from single-celled bacteria to multicellular mammals like you and me. Some viruses use RNA, not DNA, as their genetic material, but aren’t technically considered to be alive (since they cannot reproduce without help from a host).
DNA in cells
In eukaryotes, such as plants and animals, DNA is found in the nucleus ,
a specialized, membrane-bound vault in the cell, as well as in certain
other types of organelles (such as mitochondria and the chloroplasts of
plants). In prokaryotes, such as bacteria, the DNA is not enclosed in a
membranous envelope, although it's located in a specialized cell region
called the nucleoid.
In eukaryotes, DNA is typically broken up into a number of very long,
linear pieces called chromosomes , while in prokaryotes such as
bacteria, chromosomes are much smaller and often circular (ring-
shaped). A chromosome may contain tens of thousands of genes , each
providing instructions on how to make a particular product needed by
the cell.
From DNA to RNA to proteins
Many genes encode protein products, meaning that they specify the
sequence of amino acids used to build a particular protein. Before this
information can be used for protein synthesis, however, an RNA copy
(transcript) of the gene must first be made. This type of RNA is called
a messenger RNA ( mRNA ), as it serves as a messenger between DNA
and the ribosomes, molecular machines that read mRNA sequences
and use them to build proteins. This progression from DNA to RNA to
protein is called the “central dogma” of molecular biology.
Importantly, not all genes encode protein products. For instance, some
genes specify ribosomal RNAs ( rRNAs ), which serve as structural
components of ribosomes, or transfer RNAs ( tRNAs ), cloverleaf-
shaped RNA molecules that bring amino acids to the ribosome for
protein synthesis. Still other RNA molecules, such as
tiny microRNAs ( miRNAs ), act as regulators of other genes, and new
types of non-protein-coding RNAs are being discovered all the time.
Image of the components of DNA and RNA, including the sugar (deoxyribose or ribose), phosphate group, and nitrogenous base. Bases include the pyrimidine bases (cytosine, thymine in DNA, and uracil in RNA, one ring) and the purine bases (adenine and guanine, two rings). The phosphate group is attached to the 5' carbon. The 2' carbon bears a hydroxyl group in ribose, but no hydroxyl (just hydrogen) in deoxyribose. _ Nitrogenous bases The nitrogenous bases of nucleotides are organic (carbon-based) molecules made up of nitrogen-containing ring structures. Each nucleotide in DNA contains one of four possible nitrogenous bases: adenine (A), guanine (G) cytosine (C), and thymine (T). Adenine and guanine are purines , meaning that their structures contain two fused carbon-nitrogen rings. Cytosine and thymine, in contrast, are pyrimidines and have a single carbon-nitrogen ring. RNA nucleotides may also bear adenine, guanine and cytosine bases, but instead of thymine they have another pyrimidine base called uracil (U). As shown in the figure above, each base has a unique structure, with its own set of functional groups attached to the ring structure. In molecular biology shorthand, the nitrogenous bases are often just referred to by their one-letter symbols, A, T, G, C, and U. DNA contains A, T, G, and C, while RNA contains A, U, G, and C (that is, U is swapped in for T). Sugars
In addition to having slightly different sets of bases, DNA and RNA nucleotides also have slightly different sugars. The five-carbon sugar in DNA is called deoxyribose , while in RNA, the sugar is ribose. These two are very similar in structure, with just one difference: the second carbon of ribose bears a hydroxyl group, while the equivalent carbon of deoxyribose has a hydrogen instead. The carbon atoms of a nucleotide’s sugar molecule are numbered as 1′, 2′, 3′, 4′, and 5′ (1′ is read as “one prime”), as shown in the figure above. In a nucleotide, the sugar occupies a central position, with the base attached to its 1′ carbon and the phosphate group (or groups) attached to its 5′ carbon. Phosphate Nucleotides may have a single phosphate group, or a chain of up to three phosphate groups, attached to the 5’ carbon of the sugar. Some chemistry sources use the term “nucleotide” only for the single-phosphate case, but in molecular biology, the broader definition is generally accepted[^1] In a cell, a nucleotide about to be added to the end of a polynucleotide chain will bear a series of three phosphate groups. When the nucleotide joins the growing DNA or RNA chain, it loses two phosphate groups. So, in a chain of DNA or RNA, each nucleotide has just one phosphate group. Polynucleotide chains A consequence of the structure of nucleotides is that a polynucleotide chain has directionality – that is, it has two ends that are different from each other. At the 5’ end , or beginning, of the chain, the 5’ phosphate group of the first nucleotide in the chain sticks out. At the other end, called the 3’ end , the
The two strands of the helix run in opposite directions, meaning that the 5′ end of one strand is paired up with the 3′ end of its matching strand. (This is referred to as antiparallel orientation and is important for the copying of DNA.) So, can any two bases decide to get together and form a pair in the double helix? The answer is a definite no. Because of the sizes and functional groups of the bases, base pairing is highly specific: A can only pair with T, and G can only pair with C, as shown below. This means that the two strands of a DNA double helix have a very predictable relationship to each other. For instance, if you know that the sequence of one strand is 5’-AATTGGCC- 3’, the complementary strand must have the sequence 3’-TTAACCGG-5’. This allows each base to match up with its partner:
5'-AATTGGCC-3' 3'-TTAACCGG-5'
These two strands are complementary, with each base in one sticking to its partner on the other. The A-T pairs are connected by two hydrogen bonds, while the G-C pairs are connected by three hydrogen bonds. When two DNA sequences match in this way, such that they can stick to each other in an antiparallel fashion and form a helix, they are said to be complementary.
Hydrogen bonding between complementary bases holds DNA strands together in a double helix of antiparallel strands. Thymine forms two hydrogen bonds with adenine, and guanine forms three hydrogen bonds with cytosine. Properties of RNA Ribonucleic acid (RNA), unlike DNA, is usually single-stranded. A nucleotide in an RNA chain will contain ribose (the five-carbon sugar), one of the four nitrogenous bases (A, U, G, or C), and a phosphate group. Here, we'll take a look at four major types of RNA: messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), and regulatory RNAs. Messenger RNA (mRNA) Messenger RNA ( mRNA ) is an intermediate between a protein-coding gene and its protein product. If a cell needs to make a particular protein, the gene encoding the protein will be turned “on,” meaning an RNA-polymerizing enzyme will come and make an RNA copy, or transcript, of the gene’s DNA sequence. The transcript carries the same information as the DNA sequence
read out. Some rRNAs also act as enzymes, meaning that they help
accelerate (catalyze) chemical reactions – in this case, the formation of
bonds that link amino acids to form a protein. RNAs that act as enzymes
are known as ribozymes.
Transfer RNAs ( tRNAs ) are also involved in protein synthesis, but their
job is to act as carriers – to bring amino acids to the ribosome, ensuring
that the amino acid added to the chain is the one specified by the
mRNA. Transfer RNAs consist of a single strand of RNA, but this strand
has complementary segments that stick together to make double-
stranded regions. This base-pairing creates a complex 3D structure
important to the function of the molecule.
Structure of a tRNA. The overall molecule has a shape somewhat like
an L.
Regulatory RNA (miRNAs and siRNAs) Some types of non-coding RNAs (RNAs that do not encode proteins) help regulate the expression of other genes. Such RNAs may be called regulatory RNAs. For example, microRNAs ( miRNAs ) and small interfering RNAs siRNAs are small regulatory RNA molecules about 22 nucleotides long. They bind to specific mRNA molecules (with partly or fully complementary sequences) and reduce their stability or interfere with their translation, providing a way for the cell to decrease or fine-tune levels of these mRNAs.
