Page 53 - Academic Press Encyclopedia of Physical Science and Technology 3rd Molecular Biology

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Encyclopedia of Physical Science and Technology EN006H-655 June 29, 2001 21:21

502 Gene Expression, Regulation of

the human genome suggests a total gene number slightly tion of eukaryotic genes encode for multiple proteins (see
more than 20,000. Although this estimate may be too low, Section V).
it appears unlikely, based on other measurements, that the
number of genes in humans will exceed 50,000. At a first,
and even a second, glance this small difference in the num- II. DEFINITION OF A
ber of genes makes it difficult to understand why humans TRANSCRIPTION UNIT
and bacteria are so different from each other.
The past decade has seen an explosive increase in in- A transcription unit represents the combination of regu-
formation about regulation of gene expression. This re- latory and coding DNA sequences that together make up
view summarizes some of the general themes that have an expressible unit, whose expression leads to synthesis
emerged. It is focused on expression of protein-encoding of a gene product that often is a protein but also may be
genes in higher eukaryotes. At appropriate places a com- an RNA molecule. In prokaryotes, proteins in a specific
parison with gene expression in prokaryotes is made in an metabolic pathway are often encoded by genes that are
attempt to highlight similarities and to show differences clustered and transcribed into one polycistronic mRNA.
that might provide some answers to how mechanistic dif- A polycistronic mRNA encodes for multiple proteins. In
ferences in the regulation of genes may provide at least such mRNAs, ribosomes are recruited to internal transla-
part of the solution of to how a complex organism like tional initiation sites through an interaction between the
humans may have arisen without an enormous increase in 16S ribosomal RNA and the so-called Shine–Delgarno se-
the number of genes compared to prokaryotes. quence located immediately upstream of the translational
start codon that is used to initiate protein synthesis.
In eukaryotes, in contrast, the primary transcrip-
I. INTRODUCTION tion product is a precursor-RNA that undergoes several
posttranscriptional maturation steps before it is trans-
Expression of the genetic information has been summa- ported to the cytoplasm and presented to the ribosomes.
rized in the so-called central dogma, which postulates that Thus, the 5 end of the pre-mRNA is capped early after

the genetic information in a cell is transmitted from the transcription initiation by addition of an inverted methy-
DNA to an RNA intermediate to protein. A major differ- lated guanosine nucleotide (the m7G-cap), the pre-mRNA
ence between simple and complex organisms is the exis- is cleaved at its 3 terminus, and an approximately 250-

tence of a cell nucleus. Thus, prokaryotes, which include nucleotide poly(A) tail is added posttranscriptionally; fi-
the bacteria and the blue-green algae, do not have a nu- nally, the pre-mRNA is spliced to remove the interven-
cleus, whereas eukaryotes, which include animals, plants, ing intron sequences, and thus form the spliced mRNA
and fungi, have cells with a nucleus that encapsulates the which is transported to the cytoplasm. These posttran-
DNA. The basic mechanisms to regulate gene expression scriptional processing events give eukaryotes a unique,
in eukaryotes and prokaryotes are very similar, although very important level to control gene expression (see Sec-
eukaryotes generally use more sophisticated methods to tion V.). Furthermore, a eukaryotic mRNA usually is func-
squeeze out more information from the DNA sequence. In tionally monocistronic. This means that even if the mRNA
prokaryotes on–off switches of transcription appear to be encode for multiple open translational reading frames, the
the key mechanism to control gene activity, although other open reading frame closest to the 5 end of the mRNA

mechanisms also contribute to the control of gene expres- is typically the only one translated into protein. This re-
sion: transcriptional attenuation, transcriptional termina- sults from the fact that the eukaryotic ribosome recognizes

tions,andposttranscriptionaleffects.Ineukaryotessimilar the mRNA by binding to the modified 5 end of a mRNA
mechanisms are in operation. However, a key difference (recognizing the cap nucleotide), whereas prokaryotic ri-
between prokaryotes and eukaryotes is the extensive use bosomes recognizes internal Shine–Delgarno sequences
of RNA processing to generate a mature mRNA. Thus, in the polycistronic mRNA.
eukaryotic genes are encoded by discontinuous DNA seg- Transcription involves synthesis of an RNA chain that
ments that require a posttranscriptional maturation to pro- is identical in sequence to one of the two complemen-
duce a functional mRNA. As will be discussed later in tary DNA strands. DNA sequence elements upstream of
this review, the requirement for RNA splicing may be the initiation site for transcription make up the promoter
a key to the development of a highly differentiated or- that binds the RNA polymerase responsible for synthesis
ganism like humans. The general postulate that one gene of the precursor-RNA. Transcription can be subdivided
makes one protein was derived from genetic studies of into at least three stages: (1) initiation, which begins by
bacteriophages and does not apply to higher eukaryotes. RNA polymerase binding to the double-stranded DNA
Because of alternative RNA processing events a large frac- molecule and incorporation of the first nucleotide(s); (2)