Essential Cell Biology 5th edition

From DNA to RNA
241
5′
U1
RNA portion of snRNP base-pairs
with sequences that signal
splicing
exon 1 exon 2
U6
SPLICING
exon junction
complex
A
active site of
spliceosome
U1
U6
5′
3′
exon 1 exon 2
portion of spliced mRNA
A
ACTIVE SITE CREATED
BY U2 AND U6
A
U2
excised intron in the
form of a lariat
U2
3′
portion of
pre-mRNA
Figure 7–22 Splicing is carried out by a
collection of RNA–protein complexes
called snRNPs. Although there are five
snRNPs and about 200 additional proteins
required for splicing, only the three most
important snRNPs—called U1, U2, and
U6—are shown here. In the first steps of
splicing, U1 recognizes the 5ʹ splice site
and U2 recognizes the lariat branch-point
site through complementary base-pairing.
U6 then “re-checks” the 5ʹ splice site by
displacing U1 and base-pairing with this
intron sequence itself. This “re-reading”
step improves the accuracy of splicing by
double-checking the 5ʹ splice site before
carrying out the splicing reaction. In the
next steps, conformational changes in U2
and U6—triggered by the hydrolysis of ATP
by spliceosomal proteins (not shown)—
drive the formation of the spliceosome
active site. Once the splicing reactions
have occurred (see Figure 7–21), the
spliceosome deposits a group of RNAbinding
proteins, known as the exon
junction complex (red ), on the mRNA
to mark the splice site as successfully
completed.
The intron–exon type of gene arrangement in eukaryotes might seem
wasteful, but it does provide some important benefits. First, the transcripts
of many eukaryotic genes ECB5 can e7.21-7.22 be spliced in different ways, each of
which can produce a distinct protein. Such alternative splicing thereby
allows many different proteins to be produced from the same gene
(Figure 7–23). About 95% of human genes are thought to undergo alternative
splicing. Thus RNA splicing enables eukaryotes to increase the
already enormous coding potential of their genomes. In Chapter 9, we
will encounter another advantage of splicing—the production of novel
proteins—when we discuss how proteins evolve.
5′
3′
exon 1 exon 2 exon 3 exon 4
3′
5′
DNA
TRANSCRIPTION
exon 1 exon 2 exon 3 exon 4
5′ 3′
pre-mRNA
ALTERNATIVE SPLICING
1 2 3 4 1 2 4 1 3 4 1 4
four alternative mRNAs
Figure 7–23 Some pre-mRNAs undergo alternative RNA splicing to produce
different mRNAs and proteins from the same gene. Whereas all exons are
transcribed, they can be skipped over by the spliceosome to produce alternatively
spliced mRNAs, as shown. Such skipping occurs when the splicing signals at the
5ʹ end of one intron are paired up with the branch-point and 3ʹ end of a different
intron. An important feature of alternative splicing is that exons can be skipped
ECB5 e7.22-7.23
or included; however, their order—which is specified in the DNA sequence—cannot
be rearranged.