Page 255 - Color Atlas of Biochemistry

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246 Molecular genetics

RNA maturation are called snRNPs (small nuclear ribonucleo-
protein particles, pronounced “snurps”).
Before the hnRNA produced by RNA polymer- SnRNPs occur in five different forms (U1, U2,
aseII (seep. 242)can leavethe nucleus in U4, U5, and U6). They consist of numerous
order to serve as a template for protein syn- proteins and one molecule of snRNA each
thesis in the cytoplasm, it has to undergo (see p. 82).
several modifications first. Even during tran- To ensure that the RNA message is not
scription, the two ends of the transcript have destroyed, splicing has to take place in a
additional nucleotides added (A). The sections very precise fashion. The start and end of
that correspond to the intervening gene se- the hnRNA introns are recognized by a char-
quences in the DNA (introns) are then cut out acteristic sequence (...AGGT... at the 5 end or
(splicing; see B). Other transcripts—e. g., the ...[C,U]AGG... at the 3 end). Another impor-
45 S precursor of rRNA formed by polymerase tant structure is the so-called branching point
I (seep. 242)—arebroken down into smaller inside the intron. Its sequence is less con-
fragments by nucleases before export into the served than the terminal splicing sites, but it
cytoplasm. always contains one adenosine residue (A).
During splicing, the 2 -OH group of this resi-
due—supported by the spliceosome (see
A. 5 and 3 modification of mRNA
C)—attacks the phosphoric acid diester bond
Shortly after transcription begins in eukary- at the 5 endof the intron andcleaves it (b).
otes, the end of the growing RNA is blocked in Simultaneously, an unusual 2 5 bond is
several reaction steps by a structure known as formed inside the intron, which thereby takes
a“cap.” In hnRNAs, this consists of a GTP on a lasso shape (c; see formula). In the second
residuethatismethylatedatN-7 of thegua- step of the splicing process, the free 3 -OH
nine ring. The β-phosphate residue of the cap group at the end of the 5 terminal exon at-
is linked to the free 5 -OH group of the ter- tacks the A–G bond at the 3 end of the intron.
minal ribose via an ester bond. After the As a result, the two exons are linked and the
“polyadenylation signal” has been reached intron is released, still in a lasso shape (d).
(typical sequence: ...AAUAAA...; see p. 242),
a polyadenylate “tail” consisting of up to 200
AMP nucleotides is also added at the free 3 C. Spliceosome
end of the transcript. This reaction is cata- As described above, it is residues of the
lyzed by a special polyadenylate polymerase. hnRNA that carry out bond cleavage and
It is only at this point that the mRNA leaves bond formation during the splicing process.
the nucleus as a complex with RNA-binding It is therefore not a protein enzyme that acts
proteins. as a catalyst here, but rather an RNA. Catalytic
Both the cap and the poly-A tail play a vital RNAs of this type are called ribozymes (see
part in initiating eukaryotic translation (see also p. 88). The task of the spliceosomes is to
p. 250). They help position the ribosome cor- fix and orientate the reacting groups by es-
rectly on the mRNA near to the starting co- tablishing base pairings between snRNAs and
don. The protection which the additional nu- segments of the hnRNA. The probable situa-
cleotides provide against premature enzy- tion before the adenosine attack at the
matic degradation appears to be of lesser im- branching point on the 5 splicing site (see
portance. B,Fig. b) is shown schematically on the right
side of the illustration. In this phase, the U1
snRNA fixes the 5 splicing site, U2 fixes the
B. Splicing of hnRNA
branching site, and U5 fixes the ends of the
Immediately after transcription, the hnRNA two exons.
introns are removed and the exons are linked
to form a continuous coding sequence. This
process, known as splicing,is supported by
complicated RNA–protein complexes in the
nucleus, the so-called spliceosomes.The com-
ponents of these macromolecular machines

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