Chapter 2 – Orientation for the Bio-Curious  39

feature in, most importantly, various different enzymes that potentially catalyze thousands of

different biochemical reactions in thousands of biological processes in an organism, as well

as a vast range of molecular machines that drive a variety of energy-​dependent systems inside

cells, not to mention an enormous range of essential structural cellular components as well as

those involved in the detection of chemical signals both inside and outside the cell.

As Figure 2.7 suggests, there are other mechanisms for information to flow from, and to,

nucleic acids, as well as directly from protein to protein. For example, DNA replication, an

essential process, which ultimately allows daughter cells from newly divided cells to receive

a copy of the parental cell’s genetic code, involves DNA → DNA information flow. Protein

→ protein information flow can occur through the generation of prions; peptide-​based

self-​replicating structures requiring no direct transfer of information from nucleic acids,

which when incorrectly folded, are implicated in various pathologies of the brain including

Creutzfeldt–​Jakob disease, more commonly referred to by its equivalent disorder in cattle of

mad cow’s disease. Note also that there is evidence that correctly folded prions may also have

a functional role in information flow. For example, certain damaged nerve cells appear to

cleave correctly folded prion molecules whose fragments then act as a signal to neighboring

cells called “Schwann cells,” which stimulates them to repair the damaged nerve cell by manu­

facturing an increased amount of a substance called the “myelin sheath,” which is a fatty-​

based dielectric that acts as an electrical insulator around nerve cells.

RNA → DNA information flow can occur through an enzyme called “reverse tran­

scriptase,” which is utilized by some types of viruses called “retroviruses” that store their gen­

etic material in the form of RNA but then use reverse transcriptase to convert it to DNA prior

to integrating this into the DNA of a host-​infected cell (a well-​known example is the human

immunodeficiency virus [HIV]). RNA → RNA information flow can also occur through a

direct replication of RNA from an RNA template using another viral enzyme called “RNA

replicase” (studied most extensively in the polio virus).

The key stages of the principal information flow route of DNA → mRNA → protein for

the central dogma are as follows:

1 A molecular machine enzyme called “RNA polymerase” (RNAP) binds to a specific

region of the DNA at the start of a particular gene, called the promoter, whose binding

core contains a common nucleotide sequence that is present in all domains of life of

5′-​TATAAA-​3′ and is also known as the TATA box. A series of proteins called “tran­

scription factors” (TFs) can also compete for binding of the RNAP through specific

binding to the particular sequence of a given gene’s promoter region and in doing so

can specifically inhibit the binding of the RNAP in the promoter region of that gene.

This is thought to be the primary way in which the expression of proteins and peptides

from genes, that is, whether or not a gene is switched on, is regulated, in that if a

TF is bound to the promoter region, then the gene will not express any protein, and

so is switched off, whereas in the absence of any bound TF, the gene is switched on.

Expression from a single gene is thus stochastic and occurs in bursts of activity.

2 The RNAP is a good example of a multicomponent enzyme. One component is

responsible for first unwinding the double helix in the vicinity of the RNAP.

3 The RNAP then moves along one of the single strands of DNA specifically in the 3′–​

5′ direction; this process in itself is highly complex and far from completely under­

stood but is known from a variety of single-​molecule experiments performed in a

test tube environment (i.e., in vitro techniques) to require a chemical energy input

from the hydrolysis of ATP, resulting in molecular conformational changes to the

RNAP that fuel its movement along the DNA. The transcription speed along the

DNA varies typically from 20 to 90 nucleotides per second (though note that some

viruses can adapt the cell’s RNAP to increase its effective speed of transcription by

a factor of 20).

4 As the RNAP moves along the single strand of DNA, each nucleotide base of the DNA

is copied by generating a complementary strand of mRNA.

5 Once the RNAP reaches a special stop signal in the DNA code, the copying is stopped

and the completed mRNA is released from the RNAP.