Hoofdstuk 7: From DNA to protein: How cells read the genome
From DNA to RNA
Central dogma of molecular biology: when a particular protein is needed by the cell, the nucleotide
sequence of the appropriate segment of a DNA molecule is first copied into another type of nucleic
acid RNA (ribonucleic acid). That DNA segment is called a gene, and the resulting RNA copies are
then used to direct protein synthesis. So, the flow of genetic information in cells is from DNA to RNA
to protein. This process happens in all cells. From cells in bacteria to those in humans, they carry
their genetic information this way. Difference between RNA and DNA chemically: (1) the nucleotides
in RNA are ribonucleotides, they contain the sugar ribose rather than deoxyribose found in DNA; and
(2) although RNA, like DNA, contains the bases adenine (A), guanine (G), and cytosine (C), it contains
uracil (U) rather than thymine (T) found in DNA; and (3) while DNA in cells always occurs as a double-
stranded helix, RNA is largely single-stranded and can fold as a result.
The first step in gene expression is transcription. Transcription is the process in which RNA
polymerase uses one strand of DNA as a template to synthesize a complementary RNA sequence.
Many identical RNA copies can be made from the same gene. This successive amplification enables
cells to rapidly synthesize large amounts of protein whenever necessary. RNA molecule produced by
transcription that is complementary to one strand of DNA is called the RNA transcript. RNA
polymerase that catalyzes the process of transcription of protein codes has 2 functions: The enzym
RNA polymerase links covalently the growing RNA chain to ribonucleoside triphosphate. RNA
polymerases catalyze the formation of the phosphodiester bonds that link the nucleotides together
and form the sugar–phosphate backbone of the RNA chain. The RNA polymerase moves stepwise
along the DNA, unwinding the DNA helix just ahead to expose a new region of the template strand
for complementary base-pairing. In this way, the growing RNA chain is elongated by one nucleotide
at a time in the 5ʹ-to-3ʹ direction. The incoming ribonucleoside triphosphates (ATP, CTP, UTP, and
GTP) provide the energy needed to drive the reaction forward, analogous to the process of DNA
synthesis.
Most genes carried in a cell’s DNA specify the amino acid sequences of proteins. The RNA molecules
that specify the amino acid sequence of a protein is called messenger RNAs (mRNAs). There are
many other forms of RNA which al serve a different role. The term gene expression refers to the
process by which the information encoded in a DNA sequence is converted into a product, whether
RNA or protein, that has some effect on a cell or organism. RNA polymerase only binds tightly to a
DNA molecule when it has encountered a gene region called a promotor, this contains a specific
sequence of nucleotides that lies immediately upstream of the starting point for RNA synthesis.
Elongation continues until the enzyme encounters a second signal in the DNA, the terminator. Every
promoter has a certain polarity: it contains two different nucleotide sequences, laid out in a specific
5ʹ-to-3ʹ order, upstream of the transcriptional start site. These asymmetric sequences position the
RNA polymerase such that it binds to the promoter in the correct orientation. Because the
polymerase can only synthesize RNA in the 5ʹ-to-3ʹ direction, once the enzyme is bound it must use
the DNA strand that is oriented in the 3ʹ-to-5ʹ direction as its template.
Initiation of transcription: Type of Polymerase -> Genes Transcribed. RNA polymerase I -> most rRNA
genes. RNA polymerase II -> all protein-coding genes, miRNA genes, and genes for other noncoding
RNAs. RNA polymerase III -> tRNA genes, 5S rRNA gene, genes for many other small RNAs. RNA
polymerases require the assistance of a large set of accessory proteins to start transcription, these
are called general transcription factors. They must assemble at each promoter, along with the
polymerase.