Essential Cell Biology 5th edition

240 CHAPTER 7 From DNA to Protein: How Cells Read the Genome
sequences required for intron removal
5′ 3′
– – – AG GURAGU – – – – YURAC – .... – YYYYYYYYNCAG G – – –
exon 1
intron
exon 2
portion of
pre-mRNA
INTRON REMOVED
5′
3′
– – – AGG – – –
exon 1 exon 2
portion of
spliced mRNA
Figure 7–20 Special nucleotide sequences in a pre-mRNA transcript signal the
beginning and the end of an intron. Only the nucleotide sequences shown are
required to remove an intron; the other positions in an intron can be occupied by
any nucleotide. The special sequences are recognized primarily by small nuclear
ribonucleoproteins (snRNPs), which direct the cleavage of the RNA at the intron–
exon borders and catalyze the covalent linkage of the exon sequences. Here, in
addition to the standard symbols for nucleotides (A, C, G, U), R stands for either A
or G; Y stands for either C or U; ECB5 and N e7.19/7.20 stands for any nucleotide. The A shown in red
forms the branch point of the lariat produced in the splicing reaction shown in Figure
7–21. The distances along the RNA between the three splicing sequences are highly
variable; however, the distance between the branch point and the 5ʹ splice junction is
typically much longer than that between the 3ʹ splice junction and the branch point
(see Figure 7–21). The splicing sequences shown are from humans; similar sequences
direct RNA splicing in other eukaryotes.
introns, each intron contains a few short nucleotide sequences that act
as cues for its removal from the pre-mRNA. These special sequences are
found at or near each end of the intron and are the same or very similar in
all introns (Figure 7–20). Guided by these sequences, an elaborate splicing
machine cuts out the intron in the form of a “lariat” structure (Figure
7–21), formed by the reaction of an adenine nucleotide, highlighted in red
in both Figures 7–20 and 7–21, with the beginning of the intron.
5′
exon 1
2′ HO
A
intron sequence
portion of
3′
pre-mRNA
exon 2
Although we will not describe the splicing process in detail, it is worthwhile
to note that, unlike the other steps of mRNA production, RNA splicing is
carried out largely by RNA molecules rather than proteins. These RNA
molecules, called small nuclear RNAs (snRNAs), are packaged with
additional proteins to form small nuclear ribonucleoproteins (snRNPs, pronounced
“snurps”). The snRNPs recognize splice-site sequences through
complementary base-pairing between their RNA components and the
sequences in the pre-mRNA, and they carry out the chemistry of splicing
(Figure 7–22). RNA molecules that catalyze reactions in this way are
known as ribozymes, and we discuss them in more detail later in the
chapter. Together, these snRNPs form the core of the spliceosome, the
large assembly of RNA and protein molecules that carries out RNA splicing
in the nucleus. To watch the spliceosome in action, see Movie 7.5.
5′
OH
+
A
A
5′ 3′
lariat
3′
OH
3′
portion of spliced
pre-mRNA
Figure 7–21 An intron in a pre-mRNA molecule forms a branched
structure during RNA splicing. In the first step, the branch-point
adenine (red A) in the intron sequence attacks the 5ʹ splice site and
cuts the sugar–phosphate backbone of the RNA at this point (this is the
same A highlighted in red in Figure 7–20). In this process, the released
5ʹ end of the intron becomes covalently linked to the 2ʹ-OH group of
the ribose of the adenine nucleotide to form a branched structure. In
the second step of splicing, the free 3ʹ-OH end of the exon sequence
reacts with the start of the next exon sequence, joining the two exons
together into a continuous coding sequence. The intron is released as
a lariat structure, which is eventually degraded in the nucleus.