Gene expression is a fundamental cellular process. The basic mechanisms involved in expression of genes have been characterized at the molecular level. A major challenge is now to uncover how transcription, RNA processing and RNA export are organized within the cell nucleus, how these processes are coordinated with each other and how nuclear architecture influences gene expression and regulation. A significant contribution has come from cell biological approaches, which combine molecular techniques with microscopy methods. These studies have revealed that the mammalian cell nucleus is a complex but highly organized organelle, which contains numerous subcompartments. I discuss here how two essential nuclear processes - transcription and pre-mRNA splicing - are spatially organized and coordinated in vivo, and how this organization might contribute to the control of gene expression. The dynamic nature of nuclear proteins and compartments indicates a high degree of plasticity in the cellular organization of nuclear functions. The cellular organization of transcription and splicing suggest that the morphology of nuclear compartments is largely determined by the activities of the nucleus.

REFERENCES

Ascoli
C. A.
,
Maul
G. G.
(
1991
).
Identification of a novel nuclear domain.
J. Cell Biol
112
,
785
795
Báuren
G.
,
Wieslander
L.
(
1994
).
Splicing of Balbiani ring 1 gene pre-mRNA occurs simultaneously with transcription.
Cell
76
,
183
192
Bentley
D.
(
1999
).
Coupling RNA polymerase II transcription with pre-mRNA processing.
Curr. Opin. Cell Biol
11
,
347
351
Beyer
A. L.
,
Osheim
Y. N.
(
1988
).
Splice site selection, rate of splicing and alternative splicing on nascent transcripts.
Genes Dev
2
,
754
765
Boronenkov
I. V.
,
Loijens
J. C.
,
Umeda
M.
,
Anderson
R. A.
(
1998
).
Phosphoinositide signaling pathways in nuclei are associated with nuclear speckles containing pre-mRNA processing factors.
Mol. Biol. Cell
9
,
3547
3560
Bourquin
J. P.
,
Stagljar
I.
,
Meier
P.
,
Moosmann
P.
,
Silke
J.
,
Baechi
T.
,
Georgiev
O.
,
Schaffner
W.
(
1997
).
A serine/arginine-rich nuclear matrix cyclophilin interacts with the C-terminal domain of RNA polymerase II.
Nucl. Acids Res
25
,
2055
2061
Boveri
T.
(
1888
).
Zellen Studien.
Z. Naturw
22
,
687
882
Bridge
E.
,
Carmo-Fonseca
M.
,
Lamond
A.
,
Pettersson
U.
(
1993
).
Nuclear organization of splicing small nuclear ribonucleoproteins in adenovirus-infected cells.
J. Virol
67
,
5792
5802
Brown
K. E.
,
Guest
S. S.
,
Smale
S. T.
,
Hahm
K.
,
Merkenschlager
M.
,
Fisher
A. G.
(
1997
).
Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin.
Cell
91
,
845
854
Brown
K. E.
,
Baxter
J.
,
Graf
D.
,
Merkenschlager
M.
,
Fisher
A. G.
(
1999
).
Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division.
Mol. Cell
3
,
207
217
Busch
H.
,
Narayan
K. S.
,
Hamilton
J.
(
1967
).
Isolation of nucleoli in a medium containing spermine and magnesium acetate.
Exp. Cell Res
47
,
329
336
Cáceres
J. F.
,
Stamm
S.
,
Helfman
D. M.
,
Krainer
A. R.
(
1994
).
Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors.
Science
265
,
1706
1709
Cáceres
J. F.
,
Misteli
T.
,
Screaton
G.
,
Spector
D. L.
,
Krainer
A. R.
(
1997
).
Role of the modular domains of SR-proteins in subnuclear localization and alternative splicing specificity.
J. Cell Biol
138
,
225
238
Cáceres
J. F.
,
Screaton
G. R.
,
Krainer
A. R.
(
1998
).
A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm.
Genes Dev
12
,
55
66
Carvalho
T.
,
Almeida
F.
,
Calapez
A.
,
Lafarga
M.
,
Berciano
M. T.
,
Carmo-Fonseca
M.
(
1999
).
The spinal muscular atrophy disease gene product, SMN: A link between snRNP biogenesis and the Cajal (coiled) body.
J. Cell Biol
147
,
715
728
Cho
E.-J.
,
Takagi
T.
,
Moore
C. R.
,
Buratowski
S.
(
1997
).
mRNA capping enzyme is recruited to the transcription complex by phosphorylation of the RNA polymerase II carboxy-terminal domain.
Genes Dev
11
,
3319
3326
Cockell
M.
,
Gasser
S. M.
(
1999
).
Nuclear compartments and gene regulation.
Curr. Opin. Genet. Dev
9
,
199
205
Colwill
K.
,
Pawson
T.
,
Andrews
B.
,
Prasad
J.
,
Manley
J. L.
,
Bell
J. C.
,
Duncan
P. I.
(
1996
).
The Clk/Sty protein kinase phosphorylates splicing factors and regulates their intranuclear distribution.
EMBO J
15
,
265
275
Cooper
T. A.
,
Mattox
W.
(
1997
).
The regulation of splice-site selection, and its role in human disease.
Am. J. Hum. Genet
61
,
259
266
Corden
J. L.
,
Patturajan
M.
(
1997
).
A CTD function linking transcription to splicing.
Trends Biochem. Sci
22
,
413
416
Cramer
P.
,
Pesce
C. G.
,
Baralle
F. E.
,
Kornblihtt
A. R.
(
1997
).
Functional association between promoter structure and transcript alternative splicing.
Proc. Nat. Acad. Sci. USA
94
,
11456
11460
Cramer
P.
,
Caceres
J. F.
,
Cazalla
D.
,
Kadener
S.
,
Muro
A. F.
,
Baralle
F. E.
,
Kornblihtt
A. R.
(
1999
).
Coupling of transcription with alternative splicing: RNA pol II promoters modulate SF2/ASF and 9G8 effects on an exonic splicing enhancer.
Mol. Cell
4
,
251
258
Cremer
T.
,
Cremer
C.
,
Schneider
T.
,
Baumann
H.
,
Hens
L.
,
Kirsch-Volders
M.
(
1982
).
Analysis of chromosome positions in the interphase nucleus of Chinese hamster cells by laser-UV-microirradiation experiments.
Hum. Genet
62
,
201
209
Cremer
T.
, et al. 
(
1982
).
Rabl's model of the interphase chromosome arrangement tested in Chinese hamster cells by premature chromosome condensation and laser UV-microbeam experiments.
Hum. Genet
60
,
46
56
Croft
J. A.
,
Bridger
J. M.
,
Boyle
S.
,
Perry
P.
,
Teague
P.
,
Bickmore
W. A.
(
1999
).
Differences in the localization and morphology of chromosomes in the human nucleus.
J. Cell Biol
145
,
1119
1131
Custodio
N.
,
Carmo-Fonseca
M.
,
Geraghty
F.
,
Pereira
H.
,
Grosveld
F.
,
Antoniou
M.
(
1999
).
Inefficient processing impairs release of RNA from the site of transcription.
EMBO J
18
,
2855
2866
de The
H.
,
Lavau
C.
,
Marchio
A.
,
Chomienne
C.
,
Degos
L.
,
Dejean
A.
(
1991
).
The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR.
Cell
66
,
674
684
Dernburg
A. F.
,
Broman
K. W.
,
Fung
J. C.
,
Marshall
W. F.
,
Philips
J.
,
Agard
D. A.
,
Sedat
J. W.
(
1996
).
Perturbation of nuclear architecture by long-distance chromosome interactions.
Cell
85
,
745
759
Dirks
R. W.
,
de Pauw
E. S. D.
,
Raap
A. K.
(
1997
).
Splicing factors associate with nuclear HCMV-IE transcripts after transcriptional activation of the gene, but dissociate upon transcription inhibition: evidence for a dynamic organization of splicing factors.
J. Cell Sci
110
,
505
513
Du
L.
,
Warren
S. L.
(
1997
).
A functional interaction between the carboxy-terminal domain of RNA polymerase II and pre-mRNA splicing.
J. Cell Biol
136
,
5
18
Duncan
P. I.
,
Stojdl
D. F.
,
Marius
R. M.
,
Bell
J. C.
(
1997
).
In vivo regulation of alternative pre-mRNA splicing by the Clk1 protein kinase.
Mol. Cell. Biol
17
,
5996
6001
Duncan
P. I.
,
Stojdl
D. F.
,
Marius
R. M.
,
Scheit
K. H.
,
Bell
J. C.
(
1998
).
The Clk2 and Clk3 dual-specificity protein kinases regulate the intranuclear distribution of SR proteins and influence pre-mRNA splicing.
Exp. Cell Res
241
,
300
308
Fischer
U.
,
Liu
Q.
,
Dreyfuss
G.
(
1997
).
The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis.
Cell
90
,
1023
1029
Francastel
C.
,
Walters
M. C.
,
Groudine
M.
,
Martin
D. I. K.
(
1999
).
A functional enhancer suppresses silencing of a transgene and prevents its localization close to centromeric heterochromatin.
Cell
99
,
259
269
Frey
M. R.
,
Matera
A. G.
(
1995
).
Coiled bodies contain U7 small nuclear RNA and associate with specific DNA sequence in interphase human cells.
Proc. Nat. Acad. Sci. USA
92
,
5915
5919
Fu
X.-D.
(
1995
).
The superfamily of arginine/serine-rich splicing factors.
RNA
1
,
663
680
Gall
J. G.
,
Tsvetkov
A.
,
Wu
Z.
,
Murphy
C.
(
1995
).
Is the sphere organelle/coiled body a universal nuclear component?.
Dev. Genet
16
,
25
35
Gall
J. G.
,
Bellini
M.
,
Wu
Z.
,
Murphy
C.
(
1999
).
Assembly of the nuclear transcription and processing machinery: Cajal bodies (Coiled bodies) and transcriptosomes.
Mol. Biol. Cell
10
,
4385
4402
Gottschling
D. E.
,
Aparicio
O. M.
,
Billington
B. L.
,
Zakian
V. A.
(
1990
).
Position effect at S. cerevisiae telomeres: reversible repression of pol II transcription.
Cell
63
,
751
762
Gross
T.
,
Lutzelberger
M.
,
Weigmann
H.
,
Klingenhoff
A.
,
Shenoy
S.
,
Käufer
N.
(
1997
).
Functional analysis of the fission yeast Prp4 protein kinase involved in pre-mRNA splicing and isolation of a putative mammalian homologue.
Nucl. Acids Res
25
,
1028
35
Gui
J. F.
,
Lane
W. S.
,
Fu
X.-D.
) (
1994
).
A serine kinase regulates intracellular localization of splicing factors in the cell cycle.
Nature
369
,
678
682
Hendzel
M.
,
Kruhlak
M.
,
Bazett-Jones
D.
(
1998
).
Organization of highly acetylated chromatin around sites of heterogeneous nuclear RNA accumulation.
Mol. Biol. Cell
9
,
2491
2507
Hirose
Y.
,
Tacke
R.
,
Manley
J. L.
(
1999
).
Phosphorylated RNA polymerase II stimulates pre-mRNA splicing.
Genes Dev
13
,
1234
1239
Horowitz
D. S.
,
Krainer
A. R.
(
1994
).
Mechanisms for selecting 5splice sites in mammalian pre-mRNA splicing.
Trends Genet
10
,
100
106
Huang
S.
,
Deerinck
M. H.
,
Ellisman
M. H.
,
Spector
D. L.
(
1994
).
In vivo analysis of the stability and transport of nuclear poly(A)+RNA.
J. Cell Biol
126
,
877
899
Huang
S.
,
Spector
D. L.
(
1996
).
Intron-dependent recruitment of pre-mRNA splicing factors to sites of transcription.
J. Cell Biol
131
,
719
732
Huang
S.
,
Deerinck
T. J.
,
Ellisman
M. H.
,
Spector
D. L.
(
1997
).
The dynamic organization of the perinucleolar compartment in the cell nucleus.
J. Cell Biol
137
,
965
974
Jimenez-García
L. F.
,
Spector
D. L.
(
1993
).
In vivo evidence that transcription and splicing are coordinated by a recruiting mechanism.
Cell
73
,
47
59
Jolly
C.
,
Usson
Y.
,
Morimoto
R. I.
(
1999
).
Rapid and reversible relocalization of heat shock factor 1 within seconds to nuclear stress granules.
Proc. Nat. Acad. Sci. USA
96
,
6769
6774
Kakizuka
A.
,
Miller
W. H. J.
,
Umesono
K.
,
Warrell
R. P. J.
,
Frankel
S. R.
,
Murty
V.
,
Dmitrovsky
E.
,
Evans
R. M.
(
1991
).
Chromosomaltranslocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML.
Cell
66
,
663
674
Kim
E.
,
Du
L.
,
Bregman
D. B.
,
Warren
S. L.
(
1997
).
Splicing factors associate with hyperphosphorylated RNA polymerase II in the absence of pre-mRNA.
J. Cell Biol
136
,
19
28
Krause
S.
,
Fakan
S.
,
Weis
K.
,
Wahle
E.
(
1994
).
Immunodetection of poly(A) binding protein II in the cell nucleus.
Exp. Cell Res
214
,
75
82
Kuroyanagi
N.
,
Onogi
H.
,
Wakabayashi
T.
,
Hagiwara
M.
(
1998
).
Novel SR-protein-specific kinase, SRPK2, disassembles nuclear speckles.
Biochem. Biophys. Res. Commun
14
,
357
364
Lamond
A. I.
,
Earnshaw
W. C.
(
1998
).
Structure and function in the nucleus.
Science
280
,
547
553
Larsson
S.
,
Charlieu
J.
,
Miyagawa
K.
,
Engelkamp
D.
,
Rassoulzadegan
M.
,
Ross
A.
,
Cuzin
F.
,
van Heyningen
V.
,
Hastie
N.
(
1995
).
Subnuclear localization of WT1 in splicing or transcription factor domains is regulated by alternative splicing.
Cell
81
,
391
401
Liu
Q.
,
Dreyfuss
G.
(
1996
).
A novel nuclear structure containing the survival of motor neurons protein.
EMBO J
15
,
3555
3565
Loyer
P.
,
Trembley
J. H.
,
Lahti
J. M.
,
Kidd
V. J.
(
1998
).
The RNP protein, RNPS1, associates with specific isoforms of the p34cdc2-related PITSLRE protein kinase in vivo.
J. Cell Sci
111
,
1495
1506
Manley
J. L.
,
Tacke
R.
(
1996
).
SR proteins and splicing control.
Genes Dev
10
,
1569
1579
Marshall
W.
,
Fung
J.
,
Sedat
J.
(
1997
).
Deconstructing the nucleus: global architecture from local interactions.
Curr. Opin. Genet. Dev
7
,
259
263
Mayeda
A.
,
Krainer
A. R.
(
1992
).
Regulation of alternative pre-mRNA splicing by hnRNP A1 and splicing factor SF2.
Cell
68
,
365
375
McClintock
B.
(
1934
).
The relation of a particular chromosomal element to the development of the nucleoli in Zea mays.
Zeitschrift fur Zellforschung und mikroskopische Anatomie
21
,
294
328
McCracken
S.
, et al. 
(
1997
).
5-Capping enzymes are targeted to pre-mRNA by binding to the phosphorylated carboxy-terminal domain of RNA polymerase II.
Genes Dev
11
,
3306
3318
McCracken
S.
,
Fong
N.
,
Yankulov
K.
,
Ballantyne
S.
,
Pan
G.
,
Greenblatt
J.
,
Patterson
S. D.
,
Wickens
M.
,
Bentley
D.
(
1997
).
The C-terminal domain of RNA polymerase II couples mRNA processing to transcription.
Nature
385
,
357
361
Melcak
I.
,
Cermanova
S.
,
Jirsova
K.
,
Koberna
K.
,
Malinsky
J.
,
Raska
I.
(
2000
).
Nuclear pre-mRNA compartmentalization: trafficking of released transcripts to splicing factor reservoirs.
Mol. Biol. Cell
11
,
497
510
Melese
T.
,
Xue
Z.
(
1995
).
The nucleolus: an organelle formed by the act of building a ribosome.
Curr. Opin. Cell Biol
7
,
319
324
Mermoud
J. E.
,
Cohen
P.
,
Lamond
A. I.
(
1992
).
Ser/Thr-specific protein phosphatases are required for both catalytic steps of pre-mRNA splicing.
Nucl. Acids Res
20
,
5263
5269
Mermoud
J. E.
,
Cohen
P. T. W.
,
Lamond
A. I.
(
1994
).
Regulation of mammalian spliceosome assembly by a protein phosphorylation mechanism.
EMBO J
13
,
5679
5688
Misteli
T.
,
Spector
D. L.
(
1996
).
Serine/threonine phosphatase 1 modulates the subnuclear distribution of pre-mRNA splicing factors.
Mol. Biol. Cell
7
,
1559
1572
Misteli
T.
,
Cáceres
J. F.
,
Spector
D. L.
(
1997
).
The dynamics of a pre-mRNA splicing factor in living cells.
Nature
387
,
523
527
Misteli
T.
,
Spector
D. L.
(
1998
).
The cellular organization of gene expression.
Curr. Opin. Cell Biol
10
,
322
331
Misteli
T.
,
Caceres
J. F.
,
Clement
J. Q.
,
Krainer
A. R.
,
WIlkinson
M. F.
,
Spector
D. L.
(
1998
).
Serine phosphorylation of SR proteins is required for their recruitment to sites of transcription in vivo.
J. Cell Biol
143
,
297
307
Mintz
P. J.
,
Patterson
S. D.
,
Neuwald
A. F.
,
Spahr
C. S.
,
Spector
D. L.
(
1999
).
Purification and biochemical characterization of inerchromatin granule clusters.
EMBO J
18
,
4308
4320
Misteli
T.
(
1999
).
RNA splicing: What has phosphorylation got to do with it?.
Curr. Biol
9
,
198
200
Misteli
T.
,
Spector
D. L.
(
1999
).
RNA polymerase II targets pre-mRNA splicing factors to transcription sites in vivo.
Mol. Cell
3
,
697
305
Mortillaro
M. J.
,
Blencowe
B. J.
,
Wei
X.
,
Nakayasu
H.
,
Du
L.
,
Warren
S. L.
,
Sharp
P. A.
,
Berezny
R.
(
1996
).
A hyperphosphorylated form of the large subunit of RNA polymerase II is associated with splicing complexes and the nuclear matrix.
Proc. Nat. Acad. Sci. USA
93
,
8253
8257
Murray
M.
,
Kobayashi
R.
,
Krainer
A. R.
(
1999
).
The type 2C Ser/Thr phosphatase PP2Cgamma is a pre-mRNA splicing factor.
Genes Dev
13
,
87
97
Neugebauer
K. M.
,
Roth
M. B.
(
1997
).
Distribution of pre-mRNA splicing factors at sites of RNA polymerase II transcription.
Genes Dev
11
,
1148
1159
Ochs
R. L.
,
Stein
T. W. J.
,
Tan
E. M.
(
1994
).
Coiled bodies in the nucleolus of breast cancer cells.
J. Cell Sci
107
,
385
399
Park
P. C.
,
De Boni
U.
(
1996
).
Transposition of DNase hypersensitive chromatin to the nuclear periphery coincides temporally with nerve growth factor-induced up-regulation of gene expression in PC12 cells.
Proc. Nat. Acad. Sci. USA
93
,
11646
11651
Patturajan
M.
,
Wei
X.
,
Berezney
R.
,
Corden
J. L.
(
1998
).
A nuclear matrix protein interacts with the phosphorylated C-terminal domain of RNA polymerase II.
Mol. Cell. Biol
18
,
2406
2415
Pederson
T.
(
1998
).
Survey and summary. The plurifunctional nucleolus.
Nucl. Acids Res
17
,
3871
3876
Pederson
T.
(
2000
).
Half a century of the nuclear matrix.
Mol. Biol. Cell
11
,
799
805
Pellizzoni
L.
,
Kataoka
N.
,
Charroux
B.
,
Dreyfuss
G.
(
1998
).
A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing.
Cell
95
,
615
624
Phair
R. D.
,
Misteli
T.
(
2000
).
High mobility of proteins in the nucleus of mammalian cells.
Nature
404
,
604
609
Phelan
A.
,
Carmo-Fonseca
M.
,
McLauchlan
J.
,
Lamond
A. I.
,
Clements
J. B.
(
1993
).
A Herpes simplex virus type 1 immediate-early gene product, IE63, regulates small nuclear ribonucleoprotein distribution.
Proc. Nat. Acad. Sci. USA
90
,
9056
9060
Pinkel
D.
,
Landegent
J.
,
Collins
C.
,
Fuscoe
J.
,
Seagraves
R.
,
Lucas
J.
,
Gray
J. W.
(
1988
).
Fluorescence in-situ hybridization with human chromosome-specific libraries: detection of trisomy 21 and translocations of chromosome 4.
Proc. Nat. Acad. Sci. USA
85
,
91138
9142
Pombo
A.
,
Cuello
P.
,
Schul
W.
,
Yoon
J.-B.
,
Roeder
R. G.
,
Cook
P. R.
,
Murphy
S.
(
1998
).
Regional and temporal specialization in the nucleus: a transcriptionally-active nuclear domain rich in PTE, Oct1 and PIKA antigens associates with specific chromosomes early in the cell cycle.
EMBO J
17
,
1768
1778
Rossi
F.
, et al. 
(
1996
).
Specific phosphorylation ofSR proteins by mammalian DNA topoisomerase I.
Nature
381
,
80
82
Scheer
U.
,
Hock
R.
(
1999
).
Structure and function of the nucleolus.
Curr. Opin. Cell Biol
11
,
385
390
Schul
W.
,
van Der Kraan
I.
,
Matera
A. G.
,
van Driel
R.
,
de Jong
L.
(
1999
).
Nuclear domains enriched in RNA 3-processing factors associate with coiled bodies and histone genes in a cell cycle-dependent manner.
Mol. Biol. Cell
10
,
3815
3824
Schul
W.
,
van Driel
R.
,
de Jong
L.
(
1998
).
Coiled bodies and U2 snRNA genes adjacent to coiled bodies are enriched in factors required for snRNA transcription.
Mol. Biol. Cell
9
,
1025
1036
Schul
W.
,
van Driel
R.
,
de Jong
L.
(
1998
).
A subset of poly(A) polymerase is concentrated at sites of RNA synthesis and is associated with domains enriched in splicing factors and poly(A) RNA.
Exp. Cell Res
238
,
1
12
Siebel
C. W.
,
Feng
L.
,
Guthrie
C.
,
Fu
X. D.
(
1999
).
Conservation in budding yeast of a kinase specific for SR splicing factors.
Proc. Nat. Acad. Sci. USA
96
,
5440
5445
Sinclair
G. D.
,
Brasch
K.
(
1978
).
The reversible action of-amanitin on nuclear structure and molecular composition.
Exp. Cell Res
111
,
1
14
Smetana
K.
,
Ochs
R.
,
Lischwe
M. A.
,
Gyorkey
F.
,
Freireich
E.
,
Chudomel
V.
,
Busch
H.
(
1984
).
Immunofluorescence studies on proteins B23 and C23 in nucleoli of human lymphocytes.
Exp. Cell Res
152
,
195
203
Smith
K. P.
,
Moen
P. T.
,
Wydner
K. L.
,
Coleman
J. R.
,
Lawrence
J. B.
(
1999
).
Processing of endogenous pre-mRNAs in association with SC-35 domains is gene specific.
J. Cell Biol
144
,
617
629
Snaar
S. P.
,
Vincent
M.
,
Dirks
R. W.
(
1999
).
RNA polymerase II localizes at sites of human cytomegalovirus immediate-early RNA synthesis and processing.
J. Histochem. Cytochem
47
,
245
254
Spector
D. L.
(
1990
).
Higher order nuclear organization: three-dimensional distribution of small nuclear ribonucleoprotein particles.
Proc. Nat. Acad. Sci. USA
87
,
147
151
Spector
D. L.
,
Fu
X.-D.
,
Maniatis
T.
(
1991
).
Associations between distinct pre-mRNA splicing components and the cell nucleus.
EMBO J
10
,
3467
3481
Spector
D. L.
,
Lark
G.
,
Huang
S.
(
1992
).
Differences in snRNP localization between transformed and nontransformed cells.
Mol. Biol. Cell
3
,
555
569
Spector
D. L.
(
1993
).
Macromolecular domains within the cell nucleus.
Annu. Rev. Cell Biol
9
,
265
315
Takeuchi
M.
,
Yanagida
M.
(
1993
).
A mitotic role for a novel fission yeast protein kinase dsk1 with cell cycle stage dependent phosphorylation and localization.
Mol. Biol. Cell
4
,
247
260
Tanner
S.
,
Stagljar
I.
,
Georgiev
O.
,
Schaffner
W.
,
Bourquin
J. P.
(
1997
).
A novel SR-related protein specifically interacts with the carboxy-terminal domain (CTD) of RNA polymerase II through a conserved interaction domain.
Biol. Chem
378
,
565
571
Tao
W.
,
Levine
A. J.
(
1999
).
p19ARFstabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2.
Proc. Nat. Acad. Sci. USA
96
,
6937
6941
van der Houven van Oordt
W.
,
Diaz-Meco
M. T.
,
Lozano
J.
,
Krainer
A. R.
,
Moscat
J.
,
Cáceres
J. F.
(
2000
).
The MKK3/6-p38 signaling cascade alters the subcellular distribution of hnNRP A1 and modulates alternative splicing regulation.
J. Cell Biol
149
,
307
316
Vincent
M.
,
Lauriault
P.
,
Dubois
M. F.
,
Lavoie
S.
,
Bensaude
O.
,
Chabot
B.
(
1996
).
The nuclear matrix protein p255 is a highly phosphorylated form of RNA polymerase II largest subunit which associates with spliceosomes.
Nucl. Acids Res
24
,
4649
4652
Wang
H.-Y.
,
Lin
W.
,
Dyck
J. A.
,
Yeakley
J. M.
,
Songyang
Z.
,
Cantley
L. C.
,
Fu
X.-D.
) (
1998
).
SRPK2: A differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells.
J. Cell Biol
140
,
737
750
Wansink
D. G.
,
Schul
W.
,
van der Kraan
I.
,
van Steensel
B.
,
van Driel
R.
,
de Jong
L.
(
1993
).
Fluorescent labelling of nascent RNA reveals transcription by RNA polymerase II in domains scattered throughout the nucleus.
J. Cell Biol
122
,
282
293
Woppmann
A.
,
Will
C. L.
,
Kornstadt
U.
,
Zuo
P.
,
Manley
J. L.
,
Luhrmann
R.
(
1993
).
Identification of a snRNP-associated kinase activity that phosphorylates arginine/serine rich domains typical of splicing factors.
Nucl. Acids Res
21
,
2815
2822
Xiao
S. H.
,
Manley
J. L.
(
1997
).
Phosphorylation of the ASF/SF2 RS domain affects both protein-protein and protein-RNA interactions and is necessary for splicing.
Genes Dev
11
,
334
344
Xiao
S. H.
,
Manley
J. L.
(
1998
).
Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2.
EMBO J
17
,
6359
6367
Xing
Y.
,
Johnson
C. V.
,
Moen
P. T.
,
McNeil
J. A.
,
Lawrence
J. B.
(
1995
).
Nonrandom gene organization: Structural arrangements of specific pre-mRNA transcription and splicing with SC-35 domains.
J. Cell Biol
131
,
1635
1647
Yang
X.
,
Bani
M. R.
,
Lu
S. J.
,
Rowan
S.
,
Ben-David
Y.
,
Chabot
B.
(
1994
).
The A1 and A1B proteins of heterogeneous nuclear ribonucleoparticles modulate 5splice site selection in vivo.
Proc. Nat. Acad. Sci. USA
91
,
6924
6928
Yeakley
J. M.
,
Tronchere
H.
,
Olesen
J.
,
Dyck
J. A.
,
Wang
H. Y.
,
Fu
X. D.
(
1999
).
Phosphorylation regulates in vivo interaction and molecular targeting of serine/arginine-rich pre-mRNA splicing factors.
J. Cell Biol
145
,
447
455
Yue
Z.
,
Maldonado
E.
,
Pillutla
R.
,
Cho
H.
,
Reinberg
D.
,
Shatkin
A. J.
(
1997
).
Mammalian capping enzyme complements mutant Saccharomyces cerevisiae lacking mRNA guanylyltransferase and selectively binds the elongating form of RNA polymerase II.
Proc. Nat. Acad. Sci. USA
94
,
12898
12903
Yuryev
A.
,
Patturajan
M.
,
Litingtung
Y.
,
Joshi
R. V.
,
Gentile
C.
,
Gebara
M.
,
Corden
J. L.
(
1996
).
The C-terminal domain of the largest subunit of RNA polymerase II interacts with a novel set of serine/arginine-rich proteins.
Proc. Nat. Acad. Sci. USA
93
,
6975
6980
Zeng
C.
,
Kim
E.
,
Warren
S. L.
,
Berget
S. M.
(
1997
).
Dynamic relocation of transcription and splicing factors dependent upon transcriptional activity.
EMBO J
16
,
1401
1412
Zhang
G.
,
Taneja
K. L.
,
Singer
R. H.
,
Green
M. R.
(
1994
).
Localization of pre-mRNA splicing in mammalian nuclei.
Nature
372
,
809
812
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