Page 125 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

284 Chapter 8 Gene Expression: The Flow of Information from DNA to RNA to Protein

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HIV and Reverse Transcription
The AIDS-causing human immunodeficiency virus (HIV) is the latent inside the host chromosome, which then copies and trans-
most intensively analyzed virus in history. From laboratory and mits the viral genome to two new cells with each cell division.
clinical studies spanning more than three decades, researchers The events of this life cycle make HIV a retrovirus: an RNA
have learned that each viral particle is a rough-edged sphere virus that after infecting a host cell copies its own single strands
consisting of an outer envelope enclosing a protein matrix, which, of RNA into double helixes of DNA, which a viral enzyme (inte-
in turn, surrounds a cut-off cone-shaped core (Fig. A). Within the grase) then integrates into a host chromosome.
core lies an enzyme-studded genome: two identical single Reverse transcription, the foundation of the retroviral life
strands of RNA associated with many molecules of an unusual cycle, is inconsistent with the one-way, DNA-to-RNA-to-protein
DNA polymerase known as reverse transcriptase. flow of genetic information. Because it was so unexpected, the
During infection, the AIDS virus binds to and injects its phenomenon of reverse transcription encountered great resis-
cone-shaped core into cells of the human immune system (Fig. B). tance in the scientific community when first reported by Howard
The virus next uses reverse transcriptase to copy its RNA ge- Temin of the University of Wisconsin and David Baltimore, then
nome into double-stranded DNA molecules in the cytoplasm of of MIT. Now, however, it is an established fact. Reverse
the host cell. The double helixes then travel to the nucleus
where another enzyme, called integrase, inserts them into a
host chromosome. Once integrated into a host-cell chromo- Figure B Life cycle of the AIDS virus
some, the viral genome can do one of two things. It can com- 3. DNA copy of 4. DNA copy of virus genome
mandeer the host cell’s protein synthesis machinery to make virus genome integrates into host
hundreds of new viral particles that bud off from the parent cell, enters nucleus. chromosome. Host
taking with them part of the cell membrane. This process some- 2. Core disintegrates, DNA
times results in the host cell’s death, which weakens the per- releasing RNA.
son’s immune system. Alternatively, the HIV genome can lie Reverse transcriptase
produces DNA from
viral RNA genome.
Figure A Structure of the AIDS virus
5. Transcription of
HIV viral particle integrated virus
makes viral RNA
Core genome.
1. Virus particles Host cell
Protein matrix
attach to host
RNA cell membrane.
6. Core forms; new
Reverse transcriptase virus particles bud
Bilipid outer layer from host cell.

succeeding nucleotides in the RNA, forming a so­called amino acid. Recent data indicate that particular eukaryotic
methylated cap (Fig. 8.12). translation initiation factors bind to the 5′ cap, while
Like the 5′ methylated cap, the 3′ end of most eukary­ poly-A binding protein associates with the tail at the 3′
otic mRNAs is not encoded directly by the gene. In a large end of the mRNA. The interaction of these proteins in
majority of eukaryotic mRNAs, the 3′ end consists of 100–200 many cases shapes the mRNA molecule into a circle.
As, referred to as a poly-A tail (Fig. 8.13). Addition of the This circularization both enhances the initial steps of
tail is a two­step process. First, a ribonuclease cleaves the translation and stabilizes the mRNA in the cytoplasm by
primary transcript to form a new 3′ end; cleavage depends increasing the length of time it can serve as a messenger.
on the sequence AAUAAA, which is found in poly­A­
containing mRNAs 11–30 nucleotides upstream of the posi­
tion where the tail is added. Next, the enzyme poly-A Removing introns from the primary transcript
polymerase adds As onto the 3′ end exposed by cleavage. by RNA splicing
Unexpectedly, both the methylated cap and the Another kind of RNA processing became apparent in the
poly­A tail are crucial for efficient translation of the late 1970s, after researchers had developed techniques that
mRNA into protein, even though neither helps specify an enabled them to analyze nucleotide sequences in both DNA