144
Alternatively Spliced Genes
even thousands of different splicing iso-
forms. Many ion channels and neurotrans-
mitter receptors have different alternative
splicing isoforms with distinct electrophys-
iological properties. Alternative splicing
regulation has a signiFcant impact on the
proper function of the nervous system, in-
cluding learning, memory, and behavior
development.
2.2
Mechanisms Underlying Alternative
Splicing Regulation
The fundamental mechanisms underlying
alternative splicing are the intricate inter-
actions among trans-acting splicing factors
and cis-elements in the pre-mRNA sub-
strates, leading to selection of different
splice sites. These cis-elements include
splice sites and splicing regulatory se-
quences (splicing enhancers or silencers).
The sizes of the exons or introns, as
well as secondary structures of the pre-
mRNA also influence splice site selection.
The highly degenerate nature of mam-
malian splicing signals and the existence of
large numbers of trans-acting factors allow
versatile
RNA–protein
and
RNA–RNA
interactions
during
different
stages
of
spliceosome assembly. Such interactions
can be modulated by both exonic and
intronic regulatory elements. The recogni-
tion of splice sites and cis-acting splicing
regulatory sequences is mediated by a net-
work of interactions between pre-mRNA
and trans-acting factors including snRNPs
and non-snRNP splicing factors. A num-
ber of splicing regulators, both positive
and negative, play important roles in al-
ternative splicing regulation (Table 3). The
Fnal outcome of alternative splicing of a
given gene, including the production and
the delicate balance of distinct isoforms,
Tab. 3
Pre-mRNA splicing regulators.
Protein name
Motifs
RNA-binding sites
A. Splicing activators
SRp75
2 RRMs, RS
SRp55
2 RRMs, RS
ESEs
SRp40
2 RRMs, RS
ASF/SF2
2 RRMs, RS
9G8
1 RRM, RS
SC35
1 RRM, RS
SRp30c
2 RRMs, RS
hTra2
1 RRM, RS
SRp20
1 RRM, RS
SRm300
RS-rich
SRm160
PWI, RS
SF1 (BBP)
ZF, KH, CCHC,
ISE
KSRP
KH
NOVA1
3 KH
(UCAUY)3
rSLM-2
KH, STAR
CUG-BP
RRMs
ISE
ETR3
3 RRMs,
ISE
Halfpint (D.m.)
RRM (homolog of PUF60)
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