From Nucleic Acids Sequences to Molecular Medicine

650 Pages·2012·7.78 MB·English

by  Juergen Brosius (auth.)

RNA Technologies
Forfurther volumes:
http://www.springer.com/series/8619
.
Volker A. Erdmann (cid:129) Jan Barciszewski
Editors
From Nucleic Acids
Sequences to Molecular
Medicine
Editors
Prof.Dr.VolkerA.Erdmann Prof.Dr.JanBarciszewski
FreeUniversityBerlin PolishAcademyofSciences
InstituteofChemistry/Biochemistry InstituteofBioorganicChemistry
Thielallee63 Z.Noskowskiego12/14
14195Berlin 61-704Poznan
Germany Poland
[email protected] [email protected]
ISBN978-3-642-27425-1 ISBN978-3-642-27426-8(eBook)
DOI10.1007/978-3-642-27426-8
SpringerHeidelbergNewYorkDordrechtLondon
LibraryofCongressControlNumber:2012940711
#Springer-VerlagBerlinHeidelberg2012
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Preface
Nucleic Acids Meet Human Genetic Medicine
With this volume of the series RNA Technologies, we aim to cover current and
important developments in RNA chemistry, RNA biology, and the application of
RNAmoleculesinmolecularmedicine.
Cellular gene expression is based on several levels of information. First the
sequenceofthecanonicaladenine,cytosine,guanosine,andthyminebasesinDNA
encodes for the primary structures of proteins through their specific base triplet
arrangements.The“CentralDogmaofMolecularBiology”taughtusthattheDNA
is transcribed into RNAs and the protein-coding messenger RNA genes are then
translated into proteins by ribosomes. For its function the ribosomes are directly
dependent upon noncoding RNAs such as ribosomal RNAs, tRNAs, and small
nuclearRNA.ItisnowevidentthatRNA,ingeneexpression,functionsfarbeyond
the established roles of these RNAs, for example, in RNA splicing and editing,
telomere maintenance, protein secretion, small-molecule sensing, and reaction
catalysis. Thus, RNA molecules play a key role in several fundamental cellular
processes,servingasacarrierofgeneticinformationand,veryimportantly,alsoas
itsregulator.
Inhumaneukaryoticcellsonlyca.1.8%ofthegenomicDNAistranscribedinto
mRNAs, while the remaining 98.2% represents the so-called noncoding DNA
sequences.Asdiscoveredoverthelast20years,alargeamountofthisnoncoding
DNArepresentsactuallynoncodingRNA.TheimportantroleofnoncodingRNAs
in cellular processes has recently become more and more apparent. How RNA
achieves its large number of different functions with a limited assortment of four
differentbuildingblocksisstillaquestionofgreatinterest,andtheanswerliesin
decipheringtheRNAstructuresatitsdifferentlevelsofcomplexity.Moredetailed
knowledgeaboutthestructuralandfunctionalpropertiesofribonucleicacids,and
how they are functioning in the cells, is still required before methods can be
developed to use these regulators in solving the problems in molecular medicine.
In this book, up-to-date studies are presented, which follow exactly this goal: to
v
vi Preface
understandthestructuresandfunctionsofRNAmoleculesandtousethisinforma-
tionforapplicationsincellularbiologyandmolecularmedicine.
Over25yearsago,thecentraldogmaofmolecularbiologywasexpandedwith
the discovery that in addition to proteins, ribonucleic acids can also exhibit enzy-
maticactivities.TheseRNAenzymes(ribozymes)spurredintensestudiesintothe
structural basis of RNA catalysis. All naturally occurring ribozymes catalyze
phosphodiestertransferorhydrolysiswithexquisitesubstratespecificity.
Thus,RNAhasreceivedincreasinginterestasatargetofchemotherapyandas
chemotherapeutic agents to be applied in molecular medicine. The demonstration
thatsyntheticoligonucleotides couldbeused tointerferewithbiologicalinforma-
tiontransferinthe1970softhelastcenturyinducedagreatinteresttoanoveltype
of therapy. Oligomeric nucleic acid-based therapeutics can be subdivided into
groups according to their target molecule: antisense oligonucleotides (ODN),
ribozymes,microRNAsinhibitors,andshortinterferingRNAs.Theseoligonucleotides
interactbyWatson–Crickbasepairingwithcellulartranscriptsleadingtotheirdegra-
dation or functional inhibition. First antisense therapies have reached the patients.
However,arequirementfortheeffectiveapplicationofantisensetherapyisbasedon
threefundamentalissues,andtheyarestability,site-specificdelivery,andnooff-target
effects.Thisis,ofcourse,alsotruefortheemploymentoftheotherRNAmolecules,
such as siRNAs, microRNAs, or different ribozymes. To overcome the stability
problems of RNA molecules in the human serum and in the cells, efforts have been
directed tochemically modify these ribonucleic acidsin such a way thatthey would
becomeresistanttocellularribonucleases.Butwiththesemodificationsonemayalso
increasetheunwantedsideeffects,sothattheproblemsofstabilityhavesofarnotbeen
optimally solved. Very promising approaches with these goals in mind are also
presentedinthisbook.
Inthecellsoligonucleotidesareknowntomodulategeneexpressionbybindingto
proteins as aptamers, and not only that, in addition, the physiological binding to
transcription factors to reduce their capacity to mediate gene transcription has also
beenobserved.Veryinterestingandpromisingarealsoantisensemoleculesthatrecruit
RNaseHorRISCfactorstomediateRNAhydrolysis.RNAinterference,forexample,
isbestknownforitsvariousrolesinposttranscriptionalgenesilencinginthecytoplasm.
Inthisvolumethereviewersdiscussthegeneralaspectsofstructureandfunction
of ribonucleic acids as indicated above. Very interesting are the results reported,
becausetheyshowhownewandverypromisingRNAregulatorscanbedeveloped
forthenextgenerationoftherapeuticagentsdirectedatvarioustypesofdiseases.
Inthebook,wecollectedchaptersongeneralaspectsofRNA,itsstability,and
chemical modification. Several reviews highlight recent progress in development
and application of antisense technologies for RNA silencing. The therapeutic
potential of ribozymes and DNAzymes is also extensively discussed. A current
knowledge on microRNA pathways in human diseases is covered in several
chapters and will help to round up the current knowledge of RNA technologies
andasthesetechnologiesmaybeappliedinthefieldoffuturemolecularmedicine.
Berlin,Germany VolkerA.Erdmann
Poznan´,Poland JanBarciszewski
Contents
RNAissance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
JuergenBrosius
NucleicAcidsasTherapeutics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
SaraswatPushpendra,PareekArvind,andBhandariAnil
ThioEffectsasaToolforMechanisticStudiesoftheCleavage
ofRNAPhosphodiesterBonds:TheChemicalBasis. . . . . . . . . . . . . . 47
MikkoOra,TuomasL€onnberg,andHarriL€onnberg
Off-TargetEffectsandSafetyAspectsofPhosphorothioate
Oligonucleotides. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
MartinaStessl,ChristianR.Noe,andJohannesWinkler
OligonucleotideConjugates:Rationale,Synthesis,
andApplications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
YashveerSingh,PierreMurat,NicolasSpinelli,andEricDefrancq
CRISPR:ABacterialImmunitySystemBasedonSmallRNAs. . . . . . 121
€
RolfWagnerandUmitPul
AntisenseTechnology:FromUniqueLaboratoryTooltoNovel
AnticancerTreatments. . . . . . . .. . . . . . . . . . .. . . . . . . . . . .. . . . . . . 145
ChristineDiCresce,ColinWay,MateuszRytelewski,SamanMalekiVareki,
SuprithaNilam,MarkD.Vincent,JamesKoropatnick,andPeterJ.Ferguson
Antisense-MediatedReductionofEukaryoticNoncodingRNAs. . . . . 191
Xue-haiLiang,TimothyA.Vickers,andStanleyT.Crooke
AntisenseOligonucleotidesintheTreatmentofMalignantGliomas. . 215
GerardoCaruso,MariellaCaffo,GiuseppeRaudino,FedericaRaudino,
MarioVenza,andFrancescoTomasello
vii
viii Contents
NaturalAntisenseTranscriptsMediateRegulation
ofGeneExpression.. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . . .. . . .. . 247
MarcoMagistriandMohammadAliFaghihi
ActivationandDeactivationofAntisenseandRNAInterference
FunctionwithLight. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
JeaneM.GovanandAlexanderDeiters
RibozymesasMolecularBiologyReagents. . . . . . . . . . . . . . . . . . . . . . 293
SanchitaBhadra,ArtiPothukuchy,andAndrewEllington
RNATechnologiesforMitochondrialGenetics. . . . . . . . . . . . . . . . . . 313
Andre´ Dietrich,KatarzynaRolle,MartaGabryelska,ElizaWyszko,
RomainVal,MaciejSzymanski,ClarisseValentin,AnneCosset,
andJanBarciszewski
RNA-BasedTherapiesforInheritedMetabolicDiseases. . . . . . . . . . . 357
Bele´nPe´rez,MagdalenaUgarte,andLourdesR.Desviat
RNA-CleavingDNAEnzymesandTheirPotentialTherapeutic
ApplicationsasAntibacterialandAntiviralAgents. . . . . . . . . . . . . . . 371
P.I.PradeepkumarandClaudiaH€obartner
HammerheadRibozymesAgainstVirusandViroidRNAs.. . . . . .. . . 411
AlbertoCarbonell,RicardoFlores,andSelmaGago
SuppressionofHepatitisCViralGenomeReplication
withRNA-CleavingDeoxyribozyme. . . . . . . . . . . . . . . . . . . . . . . . . . . 429
Dal-HeeMinandDong-EunKim
DesignofSyntheticshRNAsforTargetingHepatitisC:
ANewApproachtoAntiviralTherapeutics. . . . . . . . . . . . . . . . . . . . . 453
BrianH.JohnstonandQingGe
TheDiverseActiveSitesinSplicing,Debranching,andMicroRNA
ProcessingAroundRNAPhosphodiesterBonds. . . . . . . . . . . . . . . . . . 475
SouravKumarDey,EduardoParedes,MollyEvans,andSubhaR.Das
MicroRNAsandTheirAntagonistsasNovelTherapeutics. . . . . . . . . 503
JeppeVinther,JakobLewinRukov,andNoamShomron
microRNAsinHumanDiseasesandViralInfections. . . . . . . . . . . . . . 525
AlessandraMescalchinandTobiasRestle
DysregulationofMicroRNAExpressionandHumanDiseases?. . . . . . 553
To-HaThai
NoncodingRNAs:IdentificationofCancer-Associated
MicroRNAs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 573
MullerFabbriandGeorgeA.Calin
Contents ix
TargetingNon-codingRNAsforCancerTherapy. . . . . . . . . . . . . . . . 589
SatyaK.KotaandSavithriBalasubramanian
MicroRNAPathwaysinDrosophila. . . . . . . . . . . . . . . . . . . . . . . . . . . 611
GeetanjaliChawlaandNicholasS.Sokol
Viroids:TheSmallestKnownInfectiousAgentsCause
AccumulationofViroid-SpecificSmallRNAs. . . . . . . . . . . . . . . . . . . 629
JaroslavMatousˇek,DetlevRiesner,andGerhardSteger
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 645