Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 289
The Multifunctional HnRNP A1 Protein in the Regulation of the
Cyp2a5 Gene
Connecting Transcriptional and Posttranscriptional Processes
BY
TINA GLISOVIC
ACTA UNIVERSITATIS UPSALIENSIS UPPSALA 2003
$ISSERTATION
"IOCHEMISTRY
!"342!#4
'LISOVIC
#YPA
VERSITATIS 0HARMACY
4HE POSTTRANSCRIPTIONALLY PYRAZOLE THE REGION
4HE ITS THE POSTTRANSCRIPTIONAL
4HE RIBONUCLEOPROTEIN OVEREXPRESSING
!
#YPA
4HE TO A FOR TO TRANSCRIPTION M2.!
4REATING INDUCER SHIFT INTERACTS OF
)N INHIBITION
#90!
AND
4HE REGULATION POSTTRANSCRIPTIONAL Ú
)33.
)3".
4INA 5NIVERSITY
7RP\SDUHQWV
,IST
4HIS 2OMAN
) 2AFFALLI -ATHIEU (ETEROGENEOUS BIOTIC INDUCIBLE
)) 'LISOVIC )NTERPLAY
#90!
))) 'LISOVIC
&
REGULATION
)6 'LISOVIC EXPRESSION CELLS
-ANUSCRIPT
2EPRINTS
!BBREVIATIONS
! (N2.0
! (N2.0
!CT$ !CTINOMYCIN
!H !RYLHYDROCARBON
!2% !5
!RG !RGININE
"2 "ALBIANI
C!-0 !DENOSINE
#AP
#!2 #ONSTITUTIVELY
#03& #LEAVAGE POLYADENYLATION
#3 #ONSENSUS
#4$ #ARBOXY TERMINAL
#90 #YTOCHROME
$2" DICHLORO BETA D RIBOFURANOSYL BENZIMIDAZOLE
%*# %XON
%-3! %LECTROPHORETIC
'- #3& 'RANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR 'LY 'LYCINE
(N2.0 (ETEROGENEOUS )LE )SOLEUCINE
K$A +ILODALTON +( + ,03 ,IPOPOLYSACCHARIDE -!2 -ATRIX -(# -AJOR -(6 -OUSE
M2.0 -ESSENGER .%3 .UCLEAR .,3 .UCLEAR .-$ .ONSENSE MEDIATED .0# .UCLEAR
NT .UCLEOTIDE 0" 0HENOBARBITAL 0HE 0HENYLALANINE
0OLY! 0OLYADENOSINE 00!2 0EROXISOME 2"$ 2.! BINDING
2.! 2.!
2.0 2IBONUCLEOPROTEIN 22- 2.!
243 2.!
282 2ETINOID
SN2.0 3MALL 32 3ERINE 4YR 4YROSINE
542 5NTRANSLATED
#ONTENTS
NUCLEAR
#YPA
#YPA
#YPA
THE
HNRNPA
#" #"
0APER
)N DISCOVERY COMPLETION OF NATURE
4HE DOGMA
$.! WITH EDITING GENE
4HE INTERMEDIARY DOGMATIC ACTIVATED OF TRANSPORT
3IMILARLY HAVE AND DECAY HAVE BUT
(OWEVER SHUTTLING COMPARTMENTS
EXPRESSION EVENTS
)N
!
)N THE
$$$$$
3RO,,WUDQVFULSWLRQ 3UHP51$
3URFHVVLQJ
&DSSLQJ 6SOLFLQJ 3RO\DGHQ\ODWLRQ
P51$
$$$$$
P51$
7UDQVODWLRQ
1
&
'HJUDGDWLRQ
SURWHLQV /RFDOL]DWLRQ
3URWHLQ
'1$
1XFOHXV
&\WRSODVP
4HE PATHWAY
PROCESS MOST
(OWEVER TEMPLATE SYNTHESIS
TO 4HESE FORMATION INCREASED
)N EXPRESSION COMPLEX
MEDIATES ULTIMATELY
&IGURE
4RANSCRIPTION
%UKARYOTES ALL
POL T2.!
)N THROUGH OCTAMER STATE OF BY TRANSCRIPTION TRIGGER
HISTONE ACETYL TRANSFERASES UNFOLDING FACTORS
TERMINATION
4HE TRANSCRIBED SEQUENCE 2.!
BEGIN
REGULATORY REGIONS
ACTIVATE WHERE INTERACTIONS ACTIVATORS TYPES
INACTIVE
&IGURE 3MALE
+LVWRQHV '1$
51$SRO,,DQGJHQHUDO WUDQVFULSWLRQIDFWRUV
&RUH SURPRWHU
&RDFWLYDWRUV
1XFOHRVRPH
$FWLYDWRUV
0RE M2.!
-OST EVIDENCE ))4HE OF POL PHOSPHORYLATION SIGNAL DEPHOSPHORYLATION IN
#4$
HYPERPHOSPHORYLATED
OF EFlCIENCY
#APPING
#AP' IS A METHYLTRANSFERASE
#4$
REACHED
SWITCH MINIMIZES THE
3PLICING
%UKARYOTIC
INTRONS
EXONS MACROMOLECULAR lVE SN2.0 PROTEIN M2.!
4RANSCRIPTS
ARE
EXPRESSION SPLICING
$URING WITH MEDIATED
DEFECTIVE PROTEINS PROTEINS
!LTERNATIVE PROTEIN EXTREME SPLICED NUMBER
0OLYADENYLATION
)N THE UPSTREAM DOWNSTREAM POLY!
THE OPEN NECESSARY SPECIlCITY TO LENGTH
!S CLEAVAGE ARE
THE
DOMAIN
,IKE M2.!
AND
([RQH[RQ
MXQFWLRQ
$$$$$$
$OWHUQDWLYH51$VSOLFLQJ H[RQLQWURQH[RQLQWURQH[RQ
51$SRO,,WUDQVFULSWLRQ
$$$$$$
JHQH
SUHP51$
·&DS ·3RO\ $ WDLO
$$$$$$
VSOLFHRVRPH
51$ VSOLFLQJ
P51$ $$$$$$
&RQVWLWXWLYH51$VSOLFLQJ
P51$
UHPRYHGLQWURQV
&IGURE
#OUPLING
4HE PROCESSING PROCESSED COUPLING PROTEINS 2.! BINDING
/NCE POSTTRANSCRIPTIONAL STABILITY THE RIBONUCLEOPROTEIN THE
$8* 8$$ $$$$ Q
&DS
51$VHFRQGDU\VWUXFWXUHV
$$8$$$
·875 &RGLQJUHJLRQ ·875
3RO\ $ WDLO
3RO\DGHQ\ODWLRQ FRQVHQVXV PRWLI
&IGURE REGION CODON
M2.!
4RANSPORT EXPRESSION TRANSCRIPTION
"OTH' STRUCTURE
TIGHT SHOWED TRANSCRIPTION
THAT COUNTERPARTS
THEREFORE OF WITH PREVENTED
M2.!
4HE PROTEIN EXPRESSION
LOCALIZED LOCALIZATION WHERE
LOCALIZATION DIRECT RECOGNIZED MECHANISM
!N ALONG IS
THAT ALTHOUGH
M2.!
4HE DEGRADATION
THIS THE
ONCOGENES
! TAIL MAMMALIAN CALLED CLEAVAGE OF THE DEADENYLATION INDEPENDENT
'HDGHQ\ODWLRQLQGHSHQGHQW GHJUDGDWLRQ 'HDGHQ\ODWLRQGHSHQGHQW GHJUDGDWLRQ
3RO\ $ VKRUWHQLQJ
$8* 8$$ $$$$$$
P*
$8* 8$$ $$$
P*
'HFDSSLQJ ·WR·GHFD\
P*
$8* 8$$ $$$
·WR·GHFD\
$8* 8$$ $$$
$8* 8$$
P*
$8* 8$$ $$$$$$
P*
$8* 8$$ $$$$$$
P* P*
$8* 8$$ $$$$$$
$8* 8$$ 8$$ $$$$$$
·WR·GHFD\
'HFDSSLQJ (QGRQXFOHRO\WLF
FOHDYDJH
'HFDSSLQJ ·WR·GHFD\
·WR·GHFD\
8$$ SUHPDWXUHWHUPLQDWLRQFRGRQ
$8*
8$$
VWDUWFRGRQ WHUPLQDWLRQFRGRQ 8$$
&IGURE 0ARKER
4RANSLATION
%UKARYOTIC LEVELS
"OTH TRANSLATION
7HILE BY THAT M2.!
STRUCTURE
YEAST SHOWN
STABLE REGULATE THE
4RANSLATION EVIDENCE
P
TERMINATION CODON IS THAT
ROUND
.0#
THE RIBOSOME DEGRADATION
.-$
4HE COMMUNICATION
!S COMPLEXES PROTEINS COMPLEXES REGULATORY AGGREGATE IS 2.! PROTEIN
4HE PROCESSES
542 STATUS M2.!
APPROPRIATE INVOLVING SUGGESTING AND
2EGULATION
3EVERAL DIURNAL A ELEMENT WAS SHORT LIVED
THE M2.!S DElNED
CONTAINING
EG
AND
PROTEINS CHARACTERIZED
/NE RECEPTOR ACQUISITION IN
ABUNDANT IRON STABILITY
AND CYTOPLASMIC WITHIN OF
2EGULATION
4ISSUE SPECIlC KNOWN 542 TRANSLATION
SPECIlC
$EVELOPMENTAL FACTOR COMBINED AND CRUCIAL OF
SOURCE EXAMPLE REQUIREMENTS INHERITED TAILS SPECIlC
STABILITY
0ERTURBATIONS ONE A PROTEINS
IN MYOTONIC
ILLUSTRATE PHYSIOLOGY
AND
IN
HETEROGENEOUS
!S A CYTOPLASM
BY OR PROTEINS INmUENCE
)N BETWEEN ADVANTAGES
OF HELP PROTEINS
CYTOPLASMIC DISCRETE !LTHOUGH THIS
/NE M2.!S SET RIBONUCLEOPROTEIN
COMPLEXES PROCESSING
(E,A PRE M2.!S
lXED
-ANY RIBOSOMES 2.0 AND TRANSFORMED 4HE OF AND BUT EXPRESSION
(N2.0 PATHWAY THE
4HE 2.! BINDING MEDIATES AND THIS DOMAINS COMPOSITION
2.!
4HE HOMOLOGY
22-S EVOLUTIONARILY DOMAIN ORGANELLES
OVERALL SEQUENCES BY INTERSPERSED
^
3EVERAL OTHER AMINO
4HE 5
TRIPEPTIDE 2.! BINDING'.' DIMETHYLARGININE
4HE ACIDS 'LY 8 )LE ACID
OCTAPEPTIDE OF
!UXILIARY
! AND
IS
RICH MEDIATED THE VITRO
INTERACTION
(N2.0 REGULATION CONSTITUTIVE PROCESSING
OF
-OST BINDING
RATHER
HAVE
END
RETAINING
3OME
AND
HN2.0
4HE"
IN EXAMINED
(N2.0 OF VARIANT "
AN"
APPROXIMATELY
0ROTEOLYTIC PURIlED ABILITY
PROTEASE FROM
50
THE PARAGRAPHS
0
5**
&6
&6
1 &
550 550
83
&IGURE
.UCLEOCYTOPLASMIC
4HE
THE
NECESSARY FAILURE NUCLEAR
APPEARS IMPORT NUCLEAR
-
PATHWAY
#OUPLING OF SIGNAL THIS A
ASSOCIATED
4HE INHIBITORS
6AUTIER DISTRIBUTION EMBRYOS )N NUCLEUS
HN2.0 RESULTS ITS
89& LUUDGLDWLRQ 2VPRWLF VKRFN
FRQWURO K K
&IGURE IN)N THE
(N2.0
-ANY
3 IDENTIlED
FACTOR REGULATE OF
!
(OWEVER SPLICE
BINDING RANDOM SPLICE
SPLICING POSSESSES VARIANT
4HE"
PRE M2.!
ACTIVITY "
#OMPETITION HIGHLY 2.! BINDING
OVER CELLS
TO
#HANGES DIFFERENTIAL MANNER AND PARALLELED REPORTER
(N2.0 RECEPTOR
' PROTEINS
4ELOMERE
4ELOMERES FROM
INSTABILITY WITH
4HE GUANOSINE THE SYNTHESIZE 4ELOMERE MOIETY
3EVERAL 6ERTEBRATE 5!'''!5
WITH
HN2.0 ,A"RANCHE BIOGENESIS
HARBOURED WAS 50
REVEALED IN INDUCED STILL
BINDING ENDO
(N2.0
3TUDIES PROLIFERATING
)N
TO"
PROLIFERATING
HUMAN PASSAGES
NUCLEUS MORE
!
(N2.0
#ONSISTENT THE -(6 INFECTED TO 2.!
DEMONSTRATED REPLICATION
HN2.0
MOUSE INFECTIOUS -(6
(N2.0
!S
$.! BINDING BIND
4HYMIDINE AN KINASE CELLULAR OVEREXPRESSION 4HESE PROMOTER
-(#
SEQUENCES AS TRANSCRIBING PROTEINS
EXAMINED )) DISCLOSED
))
CONTAIN
.& g"
PHOSPHORYLATION
!
DEGRADATION
TERMINAL REQUIRED
0OSTTRANSLATIONAL
0HOSPHORYLATION IN
INDICATE THREONINE FOR c0+#
HN2.0
CORROBORATED lBROBLASTS
TO ASSOCIATED
-ETHYLATION .'.' DIMETHYLARGININE
ARGININES
THESE IT HN2.0S
STRANDED
AFFECT
IS THAT DIGESTION
IT
4HE CAN TARAZU CONSERVED
9EAST
4HE BETWEEN MUTATION CYTOPLASMIC
FOR ASSOCIATED .PL
COTRANSCRIPTIONAL MAY
(RP
!NOTHER LARVAE EASILY STUDIES M2.!
%XTENSIVE THROUGH ELONGATED THE TO POLYSOMES
4HESE FOUND
+USLVDVVRFLDWHGZLWKWKH%DOELDQL5LQJ %5 IURPJHQHWRSRO\VRPHV
%DOELDQL 5LQJ JHQH
1XFOHDU SRUH FRPSOH[ 3RO\VRPHV
%DOELDQL 5LQJ
7UDQVFULSWLRQ 7UDQVSRUW 7UDQVODWLRQ
&\WRSODVP 1XFOHXV
&IGURE EXPRESSION
4HE OF
!
GLYCINE RICH SIMILARITY
TO
NEAR
TO
MEMBERS
PROPOSED GENE
)N UNDERSTOOD
SELECTION
ALTERNATIVE IS ALTERNATIVE
! ET
PROTEIN
542 PROCESSES
OTHER M2.!
)T TRANSPORT CAN
4HE REACTIONS AND MAKES THIS CONTAIN
4HREE RESPONSIBLE HAS SUBSTRATES
4HERE DATE MECHANISMS GENE CASES
ENZYMES
7UDQVFULSWLRQ 3URFHVVLQJ
P51$
VWDELOL]DWLRQ 7UDQVODWLRQ
3URWHLQ VWDELOL]DWLRQ
1 &
$$$$$$
&IGURE
!RYLHYDROCARBON
4HE A ONLY DEMONSTRATED
!H HSP
DOMAIN
CYTOPLASM /NCE HSP
GENES
.UCLEAR
/THER RECEPTORS
082 BELONGING HETERODIMERIZATION
#!2 PHENOBARBITAL LIKE LIGANDS
4HE RECEPTOR LIGANDS
00!2 BY
BY
PROSTAGLANDIN
!LL THEIR
M2.!
#90%
FASTING FROM
INCREASE
RECENTLY IN LOOP INSULIN
PROTEIN
4HE HYDROCARBONS
ALSO
STABILITY
!H
!NOTHER HYDROXYLASE LEVELS DEXAMETHASONE
MULTIPLE DEXAMETHASONE M2.!
4HE INVESTIGATED TRANSCRIPTIONALLY
STUDY POSTTRANSCRIPTIONAL
4HE
HYDROXYLATION
NITROSAMINES
HEPATOCYTES MUCOSA
HYDROXYLASE
LIVER
ENDOGENOUS 7ITHIN
)T
TUMOURS
UNAFFECTED
#YPA
THESE 4HE SITE BINDING
$"0
DBP
7ITH INVOLVEMENT PRIMARILY
,03 M2.!
00!2_
PATHWAY
M2.!
OBSERVED
3URPRISINGLY TO TYPE
OR MEDIATED
4HE
EFFECTS EFFECTS MECHANISMS
)T WAS OF LIVER OF OXIDATIVE
REGULATION
)N DUE
4HE AND POLYRIBOSOMES M2.!
TREATMENT M2.!
4HE 4ILLOY %LLUL OLIGONUCLEOTIDES BINDING HAIRPIN LOOP
IN PROTEIN AFlNITY IMMUNOPRECIPITATION CLOSE
&IGURE
#90!
)N OF SIGNIlCANCE
3ULPDU\ VLWH RI LQWHUDFWLRQ RI WKH S\UD]ROH
LQGXFLEOH SURWHLQ
+DLUSLQORRSUHJLRQ )XOOOHQJWK·875RIWKH
&<3$P51$
4HE
s
s
#90!
s
#YPA
s PROCESSES
)
0REVIOUSLY
#YPA
HYPOTHESIZED WITH ROLE ANALOGUE
THE
IN
AND
TO CONDITIONS
4O COMPLEX HN2.0
&IGURE
$QWLERG\ + ) 3\U 3\U 3\U
N'D
&IGURE ANTI HN2.0 CROSSLINKING UNTREATED
!NOTHER K$A IS
PLQ GLJHVWLRQ
QJ WU\SVLQ
N'D
N'D
BINDING
$IGESTION DISAPPEARANCE
!
&IGURE WAS RADIOLABELLED
)N WITH OR
INVESTIGATE SPLICING
OF
HN2.0 2.! PROBE
MONOCLONAL PROTEIN HN2.0
!LTOGETHER HN2.0 M2.!
AND
OF
)T PRIMARILY ESTABLISHED
#YPA
PLAYED FOR CONTAINING LACKING TRANSFECTED
! 542 CONTAINING
P',
(OWEVER REDUCED
4HIS BINDING SITE
M2.!
THE M2.!
&IGURE
#OLLECTIVELY HIGH ELEMENT
S*/ )/ 'HOWD
&%
&%
,QWHQVLW\RIVLJQDO DUELWUDU\XQLWV
&IGURE AND AFTER
4HE M2.!
TRANSCRIPTION DEPENDENT NUCLEAR
2.!
OF IN
±-
TO PHENOMENON WAS THE
&IGURE THE
+RXUV
&<3$
*$3'+
&<3%
&WU $FW'
&IGURE HEPATOCYTES
SHOWN
4HE REGULATION FURANOSYLBENZIMIDAZOLE TREATMENT
#90!
#90!
A
!CTINOMYCIN
542
WHEREIN BE REPORTED
4HE
#"
HEPATOCYTES CORROBORATE HEPATOCYTES PARALLEL
0APER PARALLELED THE
0YRAZOLE TREATMENT
#90!
THE ASSOCIATED
STABILIZING AN ELONGATION
COULD OF AN M2.!
) PRESENT
AND
(N2.0 CAN TRANSCRIPTION
!N WITH )N SIMILARITY TRANSCRIPTIONAL
4RANSFECTION UPSTREAM OVEREXPRESSION REPORTER
PROMOTER DRIVEN ACTIVITY
&IGURE BOXED BOXES COWORKERS
START
SUREH
SUREH
SUREH
SUREH
$**$7&&7&77&$77*$$$*$&7&&&$$***7&***7*7
**7$*7$7$**&&7$7$$7&&&$*&$&7&$*$*&$*$&$&$**7**$7&7&7*7**7&7$7*7$7**$*&7
&7$**&7$**&$**$&7$&$7$*7*$$$*&&7$7&7&$$$&$$*$$$*$$$$$7**7&777&$$&77&$7$
**7$77&$77&7$777&$$$&7$$7**$77$7$*7*77&77&7&7&&7$$**&&&7$&7$7&&&7$7&$777*
**&&&&77&7&$*$**$$*7*7&7&7$*7$7&&$7*77$7*$$**$7&&$*77&7**&77&777&7$&7*7&
&7&7*7$$7*&$7$*&7&7**$*&$&77&&7&&77$*&7$&&$&$*$77&$*7&7$&7&&&7*77$$7&7*7&
$7****&&&7&&7&&7&&7&&$*7*77**&$$7*7&&&$$$&77**7*&$&$$7$*7**$7$*7&7**$**
7
*$$$7$*77*&$7$$7&$$*$&&$$$*7&&*7&&77&7*7&7&7**$7*7$7$$$$*&$$*&7$$77&$*&
&$7&$&7*7&7*7&7$7&$&&&&$&&*&&$&&$7*&7*$&&7&$**$&7&&7&&7**7**&7*&$*
4REATING ACTIVATOR
#90!
HN2.0 SIMILARITIES THE MOBILITY UNTREATED
&IGURE BOTH
(
3TRIKINGLY COMPLEX TRANSCRIPTION
SUREH
1( FWU 3% 3% 3%
$E $ ,
FWU 3% 3% 3%
$ , SUREH
)UHH SUREH
&RPSOH[ $
&RPSOH[ %
6XSHUVKLIW
/DQHV
&IGURE
.%
ANTI HN2.0 4HE
4HE THE OVEREXPRESSING OF MARKEDLY
!
#OLLECTIVELY POSTTRANSCRIPTIONAL
EXPRESSION
!
4HE PROTEINS SHUTTLES
! WHERE
GENE
#OLLECTIVELY EXPRESSION QUESTION THESE DOWNREGULATED
MAKING ENDOGENOUS WHICH 4HESE
AND EXPRESSION CYTOPLASMIC
4HE M2.!
SUGGESTS
0APERS IN PRIMARY 0"
RESULTS THE WITH OF ASSOCIATED LOCALISATION ACTIVITY CONCURRENT M2.!
EVENTS
&\WRSODVP 1XFOHXV
KQ513$
$FW ''5%
P51$GHVWDELOL]LQJSURWHLQV
&<3$P51$GHFD\
&<3$P51$ ·FDS $$$$$$$
%,QKLELWHG&\SDWUDQVFULSWLRQ
&\SD JHQH
KQ513$
$6WLPXODWHG&\SDWUDQVFULSWLRQ 1XFOHXV &\WRSODVP
&<3$P51$GHFD\
&<3$P51$ ·FDS $$$$$$$
3%
&\SD JHQH
P51$GHVWDELOL]LQJSURWHLQV
&IGURE
&%
3DVVDJHV
N'D
SURVIVAL
THE
4HE DESCRIBED TRANSFECTING THE NUCLEUS EXTRACTS THE MOLECULAR BINDING THE
&IGURE IN EARLY INDICATED
4HE COMPETITION WITH 2.! BINDING DIGESTION PASSAGE K$A
.UCLEAR IMMUNOBLOTTED POLYCLONAL ANTIBODY
IN BANDS
NUCLEAR
#90!
LIKE
4HE DELTA
EXPRESSION COMPARED CONSTRUCT NOT
S*/ )/ 'HOWD
1RUPDOL]HG5/8YDOXHV
&%
&%
(DUO\SDVVDJH&%&%FHOOV
$
%
S*/ )/ 'HOWD
1RUPDOL]HG5/8YDOXHV
&%
&%
/DWHSDVVDJH&%&%FHOOV
&IGURE
!
4HE
#"
SUGGESTED PASSAGE DEPENDENT FORCED FUNCTION
AND OF MAY
4HE NUCLEAR (N2.0 NT
)N FROM M2.! BINDING )N PYRAZOLE OBSERVED BODY INDUCES DEGRADED
)N THE
#YPA
3TUDIES EXPRESSION HN2.0 PROMOTER HN2.0 BUT HN2.0 BETWEEN
4HIS GENERAL
)T OF MEDIATED
&UTURE UNIQUE MECHANISM WELL
4HE CEUTICAL VERSITY
MEETINGS
4HIS TO
-Y MY SCIENCE ALWAYS
-Y THE VERY 9OUR
-Y A TO
+ERSTIN HUMOUR
!NGELA TIONS STUDIES
0RESENT ,INDELL
!RAYA -ARIA WORKING OF
(ANS ANYTHING
-AGNUS THE
4HE AND HECTIC
!LL
&INALLY
-Y .ATALIJA REALIZE
-Y NISAM
7LQD
7ATSON DEOXYRIBOSE
,ANDER
6ENTER
#RICK
"ALTIMORE .ATURE
4EMIN SARCOMA
0RUSINER
"ENNE -#
CONTAINS
(OLLIDAY
'LOBAL
2EV
CELLS
3PRING
AND ING
(ESSEL TARGETED POLYMERASE
RECRUITED TERMINAL
SON MERASE
IN
THE
EVENTS
AND
BETWEEN
ITS
*OURNAL
AND
MECHANISM -OL
4&))$
CHEM
"IOL
NIOU
%-"/
METAZOANS
!LY
3PATIAL
4RANSPORT
TEMPORAL
!CTIVITY DEPENDENT GETING
YEAST
TION
BASIC SKELET
OF
SEQUENCES
TION
*"
AN
%-"/
TRANSLATION
TORS
INITIATION
WITH
WITHIN
M2.!
REGION
ELEMENTS FERENT
SENGER
ING
IRON DEPENDENT
REGULATION TURNOVER
OF UNTRANSLATED
-7
LATE
LOCALIZATION
MATERNAL 5
ELONGATION MEDIATED
OF 55555!5
n
2.!
HUMAN PARTIALLY
SEQUENCE .ATL
ELEMENT
AND
TEINS
GENE
GEON PARTICLES
FUNCTION
AND
HN2.0
EXIST
SEQUENCE SPECIlC
THE
THE BINDING
HN2.0
MATIC
ING
FOR OF
(N2.0 PROTEINS
TION
2.! 2.!
AND
THE
NUCLEAR DORSOVENTRAL
INHIBITION WITH
#HEM
#
!CIDS
M2.!
EROGENEOUS
SUBSET
HN2.0
BINDING SOME
PROTEINS
NUCLEUS
BETWEEN
FUSS BINDING
HN2.0
4
TISSUE SPECIlC
AND ANOTHER
HELIX UNWINDING
STRANDED CELLS
+2
-AMMALIAN PROTEIN
!555!
4
#HEM
*
HUMAN
"IOCHEM
SEQUENCE
PENDENT
EARLY
AND P SIGNALLING TION
FAMILY
HN2.0
DOMAINS
2EGULATED
RECRUITED
ARE
!
SPLICINGS EROGENEOUS SPLICE
ELEMENT
"
REPEATS
CAL
$.!
CLEOPROTEIN TION
$ANIELS OF
TURE .AGAI
,OSS ABUNDANCE
GENES
P).+A!2&
SENESCENCE
RIBONUCLEOPROTEIN 2.!
TEIN
CLEOPROTEIN REPLICATION
EROGENEOUS WITH
!
MODULATION 2EV
TO
REGION
HN2.0!
-OL
6IRELIZIER NUS /NCOGENE
OF
TIlCATION
"IOL
CATION
' ' DIMETHY LARGININE
!RGININE
GENEOUS
"IOCHEM
PROTEINS
FROM
$
$ROSOPHILA
THE
EXPORT
$ANEHOLT THROUGH
BOUND M2.!
THE
GOUS
!CIDS
(.20!"
ISOFORMS
2.!
OF
REQUIRED
BIND SEQUENCEN
ANALYSIS ING
OF
PHYS
ACCESSION
EVOLUTION
AND
PROTEIN
LINGER THE
#ELL
TOR MODULE
REPRESSED GENE
EXPRESSION
STEROID
AND
$EV
-
A
!CAD
SUPERFAMILY
MERA 3CI
ACIDS ACTIVATED
PROSTAGLANDIN 00!2a
OF
(6
IN
OF
SCRIPTIONAL
"IOPHYS
(EP'
TION
MOUSE
M2.!
SCRIPTIONAL 0 D
IN
RESULTS
OF REDUCING
LABILE OF
,ANG BARBITAL
#YTOCHROME MOUSE
INDUCTION
LIVER 0
ALPHA
"ARTSCH INDIVIDUALS
AMINE
TITIS
#YTOCHROME
#ARCINOG
9
0!
SUMMARIZING
&ERNANDEZ 3ALGUERO IN
&6
TRANSGENIC
ESPOOR INFESTED
,ANG TION 4OXICOL
CYTOCHROME
CYTOCHROME MICE
lCATION TION
5
COUMARIN TRANSCRIPTION
CIlC
ROLE 0HARM
$ISTINCT
"IOCHEM
HYDROXYLASE
%FFECTS INJURY
K$A IBILITY
INTERACTIONS
0YRAZOLE INDUCIBLE LATED
INSERTIONS KEMIA
MODULATING -OL
AND"
IN
TERISTIC
MACROPHAGE
!555!
LIZATION OF
OF
AND
#HEM
