Small RNAs: Analysis and Regulatory Functions (Nucleic Acids and Molecular Biology, 17)

227 Pages·2005·4.27 MB·English

by  Wolfgang Nellen

Nucleic Acids and Molecular Biology
17
Series Editor
H. J. Gross
WolfgangNellen ChristianHammann (Eds.)
Small RNAs:
Analysis and Regulatory Functions
With32Figures,and6Tables
123
ProfesssorDr.WolfgangNellen
Dr.ChristianHammann
Dept.ofGenetics
UniversityofKassel
Heinrich-Plett-Str.40
34132Kassel
Germany
LibraryofCongressControlNumber:2007934513
ISSN 0933-1891
ISBN:978-3-540-74270-8 e-ISBN: 978-3-540-28130-6
Thisworkissubjecttocopyright.Allrightsarereserved,whetherthewholeorpartofthematerial
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©Springer-VerlagBerlinHeidelberg2005, 2008
Theuseofgeneraldescriptivenames,registerednames,trademarks,etc.inthispublicationdoesnot
imply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfromtherelevantpro-
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Printedonacid-freepaper 31/3150/YL-543210
Theauthorsdedicatethisvolume
tothememoryofMartinTabler,
afriendandhighlyrespectedcolleague
whodiedinatragicaccidentonApril3rd,2005.
Preface
WhenmicroRNAswerefirstdescribedin1993bythegroupsofRuvkun(Wight-
man et al., 1993) and Ambros (Lee et al., 1993) or possibly even in 1976 by
Heywood (Heywood and Kennedy, 1976), the scientific community was not
yet ready to accept RNA as a general regulator of gene expression. Small
non-codingprokaryoticRNAswereamongthefirsttodrawattentiontotheir
unusualstructuresandtheirpotentialtoreactrapidlytoenvironmentalstim-
uliandcellularchangesbyregulating genesonthepost-transcriptionallevel
(Mizunoetal.,1984).Itisthereforeappropriatetobeginthisvolumewithan
updatebyWagnerandDarfeuilleonsmall,non-codingRNAsinprokaryotes,
thatcontrolcellularprocessesonmanydifferentlevels.
More specifically, Söderbom describes approaches to identify regulatory
RNAs in silico and in vivo and concentrates on snoRNAs. Though these are
knowntoserveasguidesformodificationofrRNAandsnRNAs,furthertargets
areemerging.
The in silico search for non-coding RNAs is detailed in the contribution
ofGräfet al.whodescribeprogramstofindnon-codingRNAs inlargedata-
bases.
BoutlaandTablerdiscussthedualapproachofbioinformaticsandinvivo
experiments todefineandvalidate newmicroRNAs–adifficulttaskofgreat
importancetounderstandthisformerlyunexpectednetworkofregulationin
eukaryoticdevelopmentanddifferentiation.
Secondary structure, in particular dsRNA, has become a major focus in
gene regulation. DsRNA is a processing intermediate and recruits diverse
machineries that modify RNA, elicit enzymatic responses or guide RNA to
specific targets. In this context, the proteins that interact with dsRNA have
attractedincreasingattention.ThechapterbyHammannreviewsthefeatures
of dsRBDs and discusses the problem how target dsRNAs are guided to one
butnottheothermolecularpathwaythatcoexistinthecell.
ThefollowingtwochaptersbyBleysetal.andKuhlmannetal.concentrateon
specialaspectsoftheRNAinterferencepathway.IncontrasttothebasicRNAi
mechanism,thespreadingofdsRNAmediatedgenesilencinginanorganism
(systemicsilencing)andalongthegeneorgenome(transitivesilencing)most
likelyinvolvestheactivityofRNAdirectedRNApolymerases.Modelsonhow
these enzymes may be involved in signal generation and amplification are
VIII Preface
alsopresentedinthelatterchapterthatevaluatesdifferencesandsimilarities
betweenRNAiandantisensemediatedgenesilencing.
OnebranchoftheRNAinterferencemechanismactsinthenucleusandcon-
fers transcriptional silencing by influencing chromatin structure. Dijk et al.
reviewexperimentsthatexplainhowsmallinterferingRNAspreventtheprolif-
erationoftransposonsinthegenomeofthemodelorganismChlamydomonas.
Paulsen and co-workers extend the view on epigenetic regulation and sum-
marizeexamplesofchromatinremodellingatspecificimprintedgenesandin
dosagecompensationinthegeneralcontextofRNAinterference.Finally,Sano
andTairadescribetheapplicationofsmallartificialriboregulatorstoidentify
genefunctionsinmammaliancells.
This volume can only provide a snapshot of the rapidly developing field
of small RNA regulatory functions. New details are continuously emerging,
nevertheless, webelievethattheoverviews,speculations, methodsandmod-
els presented in this book will not only provide a summary of the current
knowledgebutalsostimulatediscussionsandideashowtofurthertacklethis
excitingareaofresearch.
Kassel,June2005 WolfgangNellen
ChristianHammann
References
HeywoodSM,KennedyDS(1976)PurificationofmyosintranslationalcontrolRNAandits
interactionwithmyosinmessengerRNA.Biochemistry15:3314–3319
LeeRC,FeinbaumRL,AmbrosV(1993)TheC.elegansheterochronicgenelin-4encodes
smallRNAswithantisensecomplementaritytolin-14.Cell75:843–854
MizunoT,ChouMY, InouyeM(1984) Auniquemechanismregulatinggeneexpression:
translationalinhibitionbyacomplementaryRNAtranscript(micRNA).ProcNatlAcad
SciUSA81:1966–1970
WightmanB,HaI,RuvkunG(1993) Posttranscriptionalregulationoftheheterochronic
genelin-14bylin-4mediatestemporalpatternformationinC.elegans.Cell75:855–862
Contents
SmallRegulatoryRNAsinBacteria
E.G.H.Wagner,F.Darfeuille . . . . . . . . . . . . . . . . . . . . . 1
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2 SearchesandDiscoveryofsRNAs . . . . . . . . . . . . . . . 2
2.1 TheEarlyYears . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.2 Modern-DaysRNAGeneSearches . . . . . . . . . . . . . . . 4
3 TheOldandNewOnes—BiologicalFunctions . . . . . . . . 5
3.1 ManysRNAsAreInvolved
inStressResponseRegulation . . . . . . . . . . . . . . . . . 7
4 What’sOutThereinOtherBacteria? . . . . . . . . . . . . . . 13
4.1 RegulationofVirulence . . . . . . . . . . . . . . . . . . . . 13
4.2 sRNAsandQuorumSensing . . . . . . . . . . . . . . . . . . 14
4.3 OtherNonE.colisRNAs . . . . . . . . . . . . . . . . . . . . 15
5 Mechanisms:AntisenseandProteinSequestration . . . . . . 15
5.1 Antisense:cis-Versustrans-Encoded . . . . . . . . . . . . . 16
5.2 Antisense:SitesofAction—CommonThemes . . . . . . . . 17
5.3 Antisense:MechanismsofInhibition—
CommonThemes? . . . . . . . . . . . . . . . . . . . . . . . 18
5.4 Antisense:ProteinHelpersRequired,AndforWhat? . . . . . 19
5.5 Antisense:theSpecificityProblem . . . . . . . . . . . . . . . 20
6 ConcludingRemarks . . . . . . . . . . . . . . . . . . . . . . 23
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
SmallNucleolarRNAs:Identification,Structure,andFunction
F.Söderbom . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 31
2 ExperimentalIsolationofncRNAs . . . . . . . . . . . . . . . 32
2.1 SpecificIsolation . . . . . . . . . . . . . . . . . . . . . . . . 32
2.2 GeneralIsolation . . . . . . . . . . . . . . . . . . . . . . . . 33
3 ComputationalApproachestoFindncRNAs . . . . . . . . . 34
4 SmallNucleolarRNAs . . . . . . . . . . . . . . . . . . . . . 35
4.1 BoxC/DsnoRNAs . . . . . . . . . . . . . . . . . . . . . . . 37
4.2 BoxH/ACAsnoRNAs. . . . . . . . . . . . . . . . . . . . . . 38
5 SmallCajal-Body-SpecificRNAs . . . . . . . . . . . . . . . . 40
X Contents
6 ProteinAssociationandFunction . . . . . . . . . . . . . . . 41
6.1 BoxC/DsnoRNPs . . . . . . . . . . . . . . . . . . . . . . . 41
6.2 BoxH/ACAsnoRNPs . . . . . . . . . . . . . . . . . . . . . . 42
7 GenomicOrganization . . . . . . . . . . . . . . . . . . . . . 43
8 ModificationGuideRNAs—TargetsandFunction . . . . . . 45
9 ConclusionandFuturePerspective . . . . . . . . . . . . . . 46
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
AComputationalApproachtoSearchforNon-CodingRNAs
inLargeGenomicData
S.Gräf,J.-H.Teune,D.Strothmann,S.Kurtz,G.Steger . . . . . . 57
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 57
2 ProbabilityofPatterns . . . . . . . . . . . . . . . . . . . . . 60
3 DesignandRefinementofPatterns . . . . . . . . . . . . . . 62
4 SearchingPatternsinLargeSequenceSets . . . . . . . . . . 68
5 WWWTools. . . . . . . . . . . . . . . . . . . . . . . . . . . 70
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
ExperimentalStrategiesfortheIdentificationandValidation
ofTargetRNAsthatAreRegulatedbymiRNAs
A.Boutla,M.Tabler . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 76
1.1 History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
1.2 Biogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
1.3 ComputerPrediction . . . . . . . . . . . . . . . . . . . . . . 78
1.4 FamiliesofmiRNAs . . . . . . . . . . . . . . . . . . . . . . . 78
1.5 TargetPredictionbyDataBaseSearch . . . . . . . . . . . . . 79
1.6 GeneticIdentification . . . . . . . . . . . . . . . . . . . . . . 79
1.7 ExperimentalStrategiesforTargetIdentification . . . . . . . 79
2 Post-TranscriptionalInhibition
ofmiRNAFunctionbyAntisenseSequences . . . . . . . . . 80
3 DirectIdentificationofTargetmRNAbyaPCRStrategy
MimickingthemiRNAInteraction . . . . . . . . . . . . . . 84
4 ValidationofmiRNA///mRNATargetPairs
bySensorConstructs . . . . . . . . . . . . . . . . . . . . . . 85
5 ConcludingRemarks . . . . . . . . . . . . . . . . . . . . . . 87
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
ProteinInteractionswithDouble-StrandedRNAinEukaryoticCells
C.Hammann . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Contents XI
2 OccurrenceandOriginofCellularDouble-StrandedRNA . . 92
2.1 DatabaseSearchesforAntisenseRNA
andExperimentalValidation . . . . . . . . . . . . . . . . . . 92
2.2 StructuralFeaturesofDouble-StrandedRNA . . . . . . . . . 94
3 ProteinInteractions. . . . . . . . . . . . . . . . . . . . . . . 96
3.1 ProteinDomainsInteracting
withDouble-StrandedRNA . . . . . . . . . . . . . . . . . . 96
3.2 MolecularArchitecture
ofdsRBD-ContainingProteins . . . . . . . . . . . . . . . . . 99
4 CellularResponsetoDouble-StrandedRNA . . . . . . . . . 107
4.1 NuclearProcesses . . . . . . . . . . . . . . . . . . . . . . . . 107
4.2 CytoplasmicProcesses . . . . . . . . . . . . . . . . . . . . . 110
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
TransitiveandSystemicRNASilencing:
BothInvolvinganRNAAmplificationMechanism?
A.Bleys,H.vanHoudt,A.Depicker . . . . . . . . . . . . . . . . . . 119
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 119
2 RNA-DependentRNAPolymerasesandRNAAmplification . 121
3 RNAAmplificationandTransitiveSilencing . . . . . . . . . 122
3.1 TransitiveSilencinginC.elegans . . . . . . . . . . . . . . . 122
3.2 TransitiveSilencinginPlants . . . . . . . . . . . . . . . . . . 124
3.3 TransitiveSilencinginFungi . . . . . . . . . . . . . . . . . . 127
4 RNAAmplificationandSystemicSilencing . . . . . . . . . . 128
4.1 SystemicSilencinginPlants . . . . . . . . . . . . . . . . . . 128
4.2 SystemicSilencinginC.elegans . . . . . . . . . . . . . . . . 132
5 AbsenceofTransitiveandSystemicRNASilencing
inDrosophilaandMammals . . . . . . . . . . . . . . . . . . 133
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
RNAInterferenceandAntisenseMediatedGeneSilencing
M.Kuhlmann,B.Popova,W.Nellen . . . . . . . . . . . . . . . . . . 141
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 141
2 PartsoftheRNAiMachine . . . . . . . . . . . . . . . . . . . 142
2.1 RNA-DirectedRNAPolymerases . . . . . . . . . . . . . . . 144
2.2 MulticopyEnhancersofRNAi . . . . . . . . . . . . . . . . . 147
2.3 InhibitorsofSilencing . . . . . . . . . . . . . . . . . . . . . 147
3 AntisenseRNAMediatedGeneSilencing . . . . . . . . . . . 149
4 AntisenseRNAandRNAi . . . . . . . . . . . . . . . . . . . 151
4.1 SmallInterferingRNAs . . . . . . . . . . . . . . . . . . . . . 151
4.2 RNA-DirectedRNAPolymerases . . . . . . . . . . . . . . . 151
4.3 HelF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
5 Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155