Alternatively Spliced Genes
139
and activation, there are a series of con-
formational rearrangements. This process
involves not only changes in the RNA con-
formation but also remodeling of snRNPs
and exchanges of protein factors. Stud-
ies over the past two decades have only
provided a sketch of this multicompo-
nent interactive process. At the catalytic
center of the functionally mature spliceo-
some, the 5
0
ss and 3
0
ss must be juxtaposed
precisely to ensure accurate cleavage and
ligation.
The classical view of spliceosome assem-
bly features stepwise interactions between
the
pre-mRNA
substrate
and
different
spliceosomal UsnRNPs. Immediately after
transcription,
nascent
pre-mRNA
tran-
scripts interact with hnRNP (heteroge-
neous nuclear ribonucleoprotein) proteins
(Table 2) to form
Hcomp
lex
.Sp
l
iceosome
assembly is initiated with the recogni-
tion of the 5
0
splice site by U1snRNP
in an ATP-independent manner. EfFcient
interaction between the U1snRNP and
5
0
splice site requires U1snRNP-speciFc
proteins (such as U-70 K) and possibly
other proteins. Recognition of the branch
site and 3
0
splice site requires cooper-
ative binding of S±1 (also named the
branch point binding protein
, BBP) to the
branch
site
and
binding
of
U2
auxil-
iary factor (U2A±65 and U2A±35 as a
Tab. 2
Human H complex proteins.
Acce. #
Protein name
Motifs
Cal. MWt
Q13151
hnRNP A0
2 RRMs
30 841
P09651
hnRNP A1**
2 RRM
38 715
P22626
hnRNP A2/B1
2 RRMs
37 430
P51991
hnRNP A3
2 RRMs
39 686
P07910
hnRNP C1/C2
1 RRM
33 299
Q14103
hnRNP D0
2 RRMs
38 434
P26599
hnRNP I/PTB**
4 RRMs
57 221
Q07244
hnRNP K
KH
50 976
P14866
hnRNP L
3 RRMs
60 187
O43390
hnRNP R
3 RRMs
70 943
AL031668
hnRNP RALY
1 RRM
32 214
P35637
FUS/hnRNP P2
1 RRM
53 426
B54857
NF-AT 90 k
2 DSRMs, ZF
73 339
AJ271745
NFAR-1
DSRM, ZF
76 033
A54857
NF-AT 45 k
DSRM, ZF
44 697
AF037448
GRY-RBP
3 RRMs
69 633
P43243
Matrin3
94 623
O43684
hBUB3
WD40s
37 155
Q15717
HuR
3 RRMs
36 062
Q92804
TAFII68
1 RRM, ZF
61 830
P16991
YB1**
COLD
35 924
P16989
DBPA
COLD
40 060
P08107
HSP70
HSP70
70 052
P11142
HSP71
HSP70
70 898
P11021
GRP78
HSP70
72 116
The H complex proteins that are involved in alternative splicing
regulation are marked with ‘‘**.’’
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