Table Of ContentIoly Kotta-Loizou Editor
RNA Damage
and Repair
RNA Damage and Repair
Ioly Kotta-Loizou
Editor
RNA Damage and Repair
Editor
IolyKotta-Loizou
ImperialCollegeLondon
London,UK
ISBN978-3-030-76570-5 ISBN978-3-030-76571-2 (eBook)
https://doi.org/10.1007/978-3-030-76571-2
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Preface
Ribonucleic acid (RNA) is a macromolecule that plays a central role in cell physi-
ology:RNAmoleculesactasintermediatesbetweendeoxyribonucleicacid(DNA),
where genetic information is stored, and proteins, which perform the necessary
functions within cells. Traditionally, the structural and functional properties of
RNA are closely linked to gene expression; however, RNA-based enzymes called
ribozymes are also involved in catalysis and small RNAs regulate key cellular
processes, such as cell growth, division, differentiation, aging, and death. RNA is
a sensitive macromolecule that can be easily damaged, by radiation, alkylating
agents and oxidative stress, similar to the widely studied DNA and protein macro-
molecules,butalsobyribonucleases,ribotoxins,andclusteredregularlyinterspaced
short palindromic repeats (CRISPR)-Cas systems which specifically target RNA.
Therefore, cells have developed mechanisms to protect and/or repair RNA mole-
cules. “RNA damage and repair,” to my knowledge the first book on this topic,
presentsanoverviewofthebiologyofRNAdamageandrepairinprokaryoticand
eukaryoticcells.Individualchapterscoverexpressionregulation,enzymology,and
thephysiologicalroleofsuchsystems,togetherwiththeirlinkstoimportanthuman
diseases.
The first three chapters focus on RNA damage and repair in prokaryotic organ-
isms,mainlybacteria.
Chapter “Endoribonucleases of the Toxin–Antitoxin Systems Induce Abortive
Infection,” describes how bacteria utilize enzymes that damage RNA to protect
themselves against bacteriophage infection and the response of bacteriophage in
thisarms race. Inthiscontext,thetoxin–antitoxin systems MazF-MazEandRnlA-
RnlB in the model organism Escherichia coli and ToxIN in the plant pathogen
Pectobacteriumatrosepticumarediscussedindetail.
Chapter “The Lifecycle of Ribosomal RNA in Bacteria,” focuses on ribosomal
(r)RNA:non-coding,ubiquitous,stable,catalyticRNAmoleculesthatplayacrucial
structuralandfunctionalroleinproteinproduction.Thecomplexcellularprocesses
regulating expression, maturation and modification of rRNA molecules and their
v
vi Preface
subsequent assembly in functional ribosomes are described together with quality
controlmechanisms,potentiallydamagingfactorsandrepairsystems.
Chapter “The Rtc RNA End Healing and Sealing System,” focuses on two
enzymesconservedinallthreekingdomsoflife:RNAligaseRtcBandRNAcyclase
RtcA.Thebiochemistryandstructureoftheseenzymesarediscussed,togetherwith
theirbiologicalroleinprokaryotesandeukaryotes,andtheirexpressionregulationin
bacteria under the control of the enhancer-binding protein RtcR and its CRISPR
associatedRossmannfolddomain.
The next three chapters focus on RNA damage and repair in eukaryotic organ-
isms,includingplants.
Chapter“OxidativeandNitrativeRNAModificationsinPlants,”illustrateshow
chemicaldamagetoRNAcausedbyreactiveoxidativeandnitrativespeciesinplant
cells plays a regulatory role in both physiological and stress induced processes.
Modified RNA transcripts containing 8-hydroxyguanine and 8-nitroguanine are
associatedwithseeddormancyandgermination,microbeinfectionandplantdefense
responses,andheavymetalinducedstress.
Chapter“TheRoleofRibonucleasesinRNADamage,Inactivation,andDegra-
dation,”describeshowcellsutilizeenzymesthattargetRNAasdefensemechanisms
to protect themselves from damaged self and foreign RNA. These mechanisms act
against defective messenger (m)RNA molecules that stall ribosomes and interfere
with translation or viral RNA molecules and immunity-related transcripts during
infection.
Chapter “Cytoplasmic mRNA Recapping: An Unexpected Form of RNA
Repair,” focuses on the 7-methylguanosine cap at the 5’ terminus of eukaryotic
mRNAs, whose presence affects translation and mRNA decay. In addition to the
established nuclear co-transcriptional capping, mRNAs may be decapped and
recapped in the cytoplasm, a process that potentially has significant implications
forthecellproteome.
ThelasttwochaptersfocusonthelinksbetweenRNAdamageandphysiological
humandiseases.
Chapter “Adenosine-to-Inosine RNA Editing: A Key RNA Processing Step
Rewriting the Transcriptome in Normal Physiology and Diseases,” illustrates how
damagetoRNAmoleculesintheformofmutationscausedbyadenosine-to-inosine
editingisregulated,togetherwithitseffectsonnumerouscellularprocessesinclud-
ing RNA silencing, splicing and polyadenylation, circadian rhythm, innate immu-
nity,apoptosis,andcancer.
Chapter “RNA-Mediated Metabolic Defects in Microsatellite Expansion Dis-
eases,” focuses on the role of RNA metabolism in neurodegenerative disorders,
such as Huntington’s disease, various forms of dystrophy, ataxia, epilepsy, and
dementia.ThemolecularmechanismsunderpinningRNAtoxicity,includingprotein
loss-of-function,proteingain-of-function,andRNAgain-of-function,arediscussed
indetail.
Preface vii
Thankstothehigh-qualitycontributionsfromalltheauthorsinvolved,Ihopethat
“RNAdamageandrepair”willbeabookusefultoalllifescientistsinterestedinthe
biology and homeostasis of RNA, coding or non-coding, intact, modified, or
cleaved, in bacteria, plants, or mammals, under physiological conditions or during
infectionanddisease.
London,UK IolyKotta-Loizou
Contents
PartI RNADamageandRepairinProkaryotes
EndoribonucleasesoftheToxin-AntitoxinSystemsInduceAbortive
Infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
YuichiOtsuka
TheLifecycleofRibosomalRNAinBacteria. . . . . . . . . . . . . . . . . . . . . 27
MariaGraziaGiulianoandChristophEngl
TheRtcRNAEndHealingandSealingSystem. . . . . . . . . . . . . . . . . . . 53
DanaiAthinaIrakleidi,HarryBeaven,MartinBuck,andIolyKotta-Loizou
PartII RNADamageandRepairinEukaryotes
OxidativeandNitrativeRNAModificationsinPlants. . . . . . . . . . . . . . . 75
JagnaChmielowska-Bąk,KarolinaIzbiańska-Jankowska,Magdalena
Arasimowicz-Jelonek,JoannaDeckert,andJolantaFloryszak-Wieczorek
TheRoleofRibonucleasesinRNADamage,Inactivation
andDegradation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
FabianHiaandOsamuTakeuchi
CytoplasmicmRNARecapping:AnUnexpectedFormofRNA
Repair. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
DanielR.Schoenberg
PartIII RNADamageinHumanDiseases
Adenosine-to-InosineRNAEditing:AKeyRNAProcessingStep
RewritingTranscriptomeinNormalPhysiologyandDiseases. . . . . . . . 133
PriyankaaPitcheshwar,HaoqingShen,JianHan,andSzeJingTang
RNA-MediatedMetabolicDefectsinMicrosatelliteExpansionDiseases. . 153
NanZhang
ix
Part I
RNA Damage and Repair in Prokaryotes
Endoribonucleases of the Toxin-Antitoxin
Systems Induce Abortive Infection
YuichiOtsuka
Abstract Acompetitivebacteria-phagecoevolutionisoftenreferredtoasan“arms
race.” On the one hand, bacteria have evolved a variety of defense mechanisms
againstphagessuchasinhibitionofphageadsorptionandcleavageofphagenucleic
acidsthroughtherestriction-modificationsystemortheCRISPR-Cassystem.Onthe
other hand, phages have also devised many means to protect themselves from
bacterial defense mechanisms. The abortive infection (Abi) system, one of the
bacterialdefensemechanisms,inhibitsphagepropagationbykillingphage-infected
cellsbeforethephagelifecycleiscompleted.Abicanbeachievedthroughthetoxin-
antitoxin(TA)system,awidespreadgeneticmoduleinprokaryotescomposedofa
toxinandthecorrespondingantitoxin.Inthissystem,thetoxininhibitsanessential
cellularprocesstoarrestcellgrowth,whiletheantitoxinneutralizesthetoxicityofa
cognatetoxin.MazFandRnlAtoxinsoftheEscherichiacoliTAsystemsandToxN
toxinoftheplantpathogenPectobacteriumatrosepticumTAsystemhavebeenwell
studiedanddemonstratedtopossessendoribonucleaseactivitiesrequiredforAbi.In
this chapter, I will discuss the functions, structures, and regulations of their
endoribonucleases. I will also discuss how these endoribonucleases induce Abi
andhowphagescounteractAbi.
Keywords Bacteria·Bacteriophages(phages)·Theabortiveinfection(Abi)·
Thetoxin-antitoxin(TA)systems·Endoribonucleases·MazF·RnlA·ToxN
Y.Otsuka(*)
DepartmentofBiochemistryandMolecularBiology,GraduateSchoolofScienceand
Engineering,SaitamaUniversity,SaitamaCity,Saitama,Japan
e-mail:[email protected]
©SpringerNatureSwitzerlandAG2021 3
I.Kotta-Loizou(ed.),RNADamageandRepair,
https://doi.org/10.1007/978-3-030-76571-2_1
