Alternatively Spliced Genes
163
using microarray approaches to examine
splicing isoforms under different physi-
ological or pathological conditions at the
genome level may be important for under-
standingtheroleofalternativepre-mRNA
splicing in the biology of mammalian cells.
The basic components of mammalian
splicing machinery are
now
character-
ized
at
the
molecular
level.
However,
the dynamic interactions among differ-
ent components of the splicing machinery
during spliceosome assembly and recog-
nition of splicing regulatory elements are
far from being understood. Little is known
about the structural basis of such multi-
component interactions. Furthermore, the
catalytic mechanisms of pre-mRNA splic-
ing remain to be elucidated.
On the basis of studies of the relatively
few model genes, a number of cis-acting
elements and trans-acting splicing regula-
tors have been identi±ed. The mechanisms
by which the splicing machinery speci±-
cally recognizes authentic versus decoy, or
pseudosplice sites remain unclear. Some
of the splicing regulatory factors are also
important players for spliceosome assem-
bly.
Spliceosomal proteins
also
play
a
role in other processes of gene regula-
tion. Further work needs to be carried out
to understand the relationship between
pre-mRNA splicing and other processes
of gene expression and regulation, in-
cluding transcription, RNA editing, RNA
transport, translational control, and post-
translational modi±cation.
Studies of human diseases caused by
splicing mutations or aberrant splicing
have signi±cantly advanced our under-
standing
of
human
genetic
diseases.
Tremendous
effort
is
still
required
to
understand pathogenetic mechanisms un-
derlying diseases caused by splicing de-
fects, to develop ef±cient diagnostic tools
and to design effective therapeutic ap-
proaches for these diseases.
Acknowledgment
We apologize to readers and our colleagues
for having referred only to reviews instead
of original research articles because of the
space limit. The work in the authors’ lab-
oratory has been generously supported by
Leukemia and Lymphoma Society, Mus-
cular Dystrophy Association, Alzheimer’s
Association, the Society for Progressive
Supranuclear Palsy, and NIH (AG17518,
GM53945 and EY014576). We thank Drs
Chris Burge, Reinhard L¨uhrmann, Robin
Reed, Phil Sharp, and Joan Steitz for
sharing information and for giving per-
missions to modify ±gures from their
previous publications. We are grateful to
Drs Edward Benz, Doug Black, James
Bruzik, Mariano Garcia-Blanco, Warren
Gish, David Ornitz, Arnold Strauss, and
members of Wu laboratory for their criti-
cal reading of the manuscript. We thank
German G. Leparc, Joe Gee Seo, and Ying
Zhang for the data bank searches and Mrs.
Angie Hantak for outstanding assistance.
See also
Genetics, Molecular Basis
of.
Bibliography
Books and Reviews
Adams, M.D.,
Rudner, D.Z.,
Rio, D.C.
(1996)
Biochemistry and regulation of pre-mRNA
splicing,
Curr. Opin. Cell. Biol.
8
(3), 331–339.
Bartel, F.,
Taubert, H.,
Harris, L.C.
(2002)
Alternative and aberrant splicing of MDM2
mRNA in human cancer,
Cancer Cell
2
(1),
9–15.
previous page 163 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 165 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off