Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

REGULATION OF GENE EXPRESSION BY NONCODING RNAs
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REGULATION OF GENE EXPRESSION BY
NONCODING RNAs
In the previous chapter, we introduced the central dogma, according to which the
flow of genetic information proceeds from DNA through RNA to protein (Figure
6–1). But we have seen throughout this book that RNA molecules perform many
critical tasks in the cell besides serving as intermediate carriers of genetic information.
Among these noncoding RNAs are the rRNA and tRNA molecules, which
are responsible for reading the genetic code and synthesizing proteins. The RNA
molecule in telomerase serves as a template for the replication of chromosome
ends, snoRNAs modify ribosomal RNA, and snRNAs carry out the major events of
RNA splicing. And we saw in the previous section that Xist RNA has an important
role in inactivating one copy of the X chromosome in females.
A series of recent discoveries has revealed that noncoding RNAs are even more
prevalent than previously imagined. We now know that such RNAs play widespread
roles in regulating gene expression and in protecting the genome from
viruses and transposable elements. These newly discovered RNAs are the subject
of this section.
Small Noncoding RNA Transcripts Regulate Many Animal and
Plant Genes Through RNA Interference
We begin our discussion with a group of short RNAs that carry out RNA interference
or RNAi. Here, short single-stranded RNAs (20–30 nucleotides) serve as
guide RNAs that selectively reorganize and bind—through base-pairing—other
RNAs in the cell. When the target is a mature mRNA, the small noncoding RNAs
can inhibit its translation or even catalyze its destruction. If the target RNA molecule
is in the process of being transcribed, the small noncoding RNA can bind to
it and direct the formation of certain types of repressive chromatin on its attached
DNA template (Figure 7–74). Three classes of small noncoding RNAs work in this
way—microRNAs (miRNAs), small interfering RNAs (siRNAs), and piwi-interacting
RNAs (piRNAs)—and we discuss them in turn in the next sections. Although
they differ in the way the short pieces of single-stranded RNA are generated, all
three types of short RNAs locate their targets through RNA–RNA base-pairing, and
they generally cause reductions in gene expression.
miRNAs Regulate mRNA Translation and Stability
Over 1000 different microRNAs (miRNAs) are produced from the human genome,
and these appear to regulate at least one-third of all human protein-coding genes.
Once made, miRNAs base-pair with specific mRNAs and fine-tune their translation
and stability. The miRNA precursors are synthesized by RNA polymerase II
and are capped and polyadenylated. They then undergo a special type of processing,
after which the miRNA (typically 23 nucleotides in length) is assembled with
a set of proteins to form an RNA-induced silencing complex or RISC. Once formed,
the RISC seeks out its target mRNAs by searching for complementary nucleotide
double-stranded
RNA
interfering RNA
processing
Argonaute or Piwi
proteins
cleavage of
target RNA
target
RNA
translational repression
and eventual destruction
of target RNA
formation of heterochromatin
on DNA from which target RNA
is being transcribed
Figure 7–74 RNA interference in
eukaryotes. Single-stranded interfering
RNAs are generated from double-stranded
RNA. They locate target RNAs through
base-pairing and, at this point, several fates
are possible, as shown. As described in
the text, there are several types of RNA
interference; the way the double-stranded
RNA is produced and processed and the
ultimate fate of the target RNA depends on
the particular system.