Macro Roles for Micrornas in the Life and Death of Neurons

ISBN-13: 9783642262043 / Angielski / Miękka / 2012 / 121 str.

Bart de Strooper

Opis

ThediscoveryofmicroRNAshasrevealedanunexpectedandspectacularadditional levelof?netuningofthegenomeandhowgenesareusedagainandagainin differentcombinationstogeneratethecomplexitythatunderliesforinstancethe brain. SincetheinitialstudiesperformedinC. elegans, wegavegoneafarwayto begintounderstandhowmicroRNApathwayscanhaveanimpactonhealthand diseaseinhuman. AlthoughmicroRNAsareabundantlyexpressedinthebrain, relativelylittleisknownaboutthemultiplefunctionsoftheseRNAmoleculesinthe nervous system. Nevertheless, we knowalready that microRNA pathways play majorrolesintheproliferation, differentiation, functionandmaintenanceofneu- nalcells. SeveralintriguingstudieshavelinkedmicroRNAsasmajorregulatorsof theneuronalphenotype, andhaveimplicatedspeci?cmicroRNAsintheregulation ofsynapseformationandplasticity. DysfunctionofmicroRNApathwaysisalso slowlyemergingasapotentialimportantcontributortothepathogenesisofmajor neurodegenerativedisorderssuchasAlzheimer'sdiseaseandParkinson'sdisease. Thesenovelinsightsappeartobeparticularpromisingfortheunderstandingofthe veryfrequentandbadlyunderstoodsporadicformsofthesediseasesascomparedto thegeneticforms. Thus, thebetterunderstandingoftheimplicationsofthisnovel ?eldofmolecularbiologyiscrucialforthebroadareaofneurosciences, fromthe fundamentalaspectstotheclinic, andfromnoveldiagnostictopotentiallythe- peuticapplicationsforsevereneurologicalandmaybepsychiatricdiseases. The presentvolumegatherscontributionstotheColloqueMedecineetRechercheonthe implicationsofmicroRNAsinneuroscienceorganizedbytheFondationIpsen, in Paris, onApril20,2009. Ithadasobjectivetobringtogetherneuroscientistsfrom differentareasofresearchtodiscusstheircurrentinsightsintothewonderfulworld ofmicroRNAs, andtohearanddiscusstheirresearchandviewsaboutmicroRNA biologyinneuronalprocessesandinbraindisorders. BartdeStrooper YvesChristen v Acknowledgments The editors wish to thank Jacqueline Mervaillie and Sonia Le Cornec for the organizationofthemeetingandMaryLynnGagefortheeditingofthebook. vii Contents Pro?lingthemicroRNAs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 KennethS. Kosik, ThalesPapagiannakopoulos, NaXu, KawtherAbu-Elneel, TsunglinLiu, andMinJeongKye TheWideVarietyofmiRNAExpressionPro?les intheDevelopingandMatureCNS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 MarikaKapsimali InteractionsbetweenmicroRNAsandTranscription FactorsintheDevelopmentandFunction oftheNervousSystem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 DavidJ. Simon AmicroRNAFeedbackCircuitinMidbrainDopamineNeurons . . . . . . . . . 27 AsaAbeliovich Fine-tuningmRNATranslationatSynapseswithmicroRNAs . . . . . . . . . . . . 35 GerhardM. Schratt NeuronalP-bodiesandTransportofmicroRNA-Repressed mRNAs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 FlorenceRage CrosstalkbetweenmicroRNAandEpigeneticRegulation inStemCells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 KeithSzulwach, ShuangChang, andPengJin microRNAsinCNSDevelopmentandNeurodegeneration: InsightsfromDrosophilaGenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 StephenM. Cohen ix x Contents DrosophilaasaModelforNeurodegenerativeDisease: RolesofRNAPathwaysinPathogenesis . . . . . . .

Spis treści

Profiling the microRNAs by Kenneth S. Kosik, Thales Papagiannakopoulos, Na Xu, Kawther Abu-Elneel, Tsunglin Liu and Min Jeong Kye.- The Wide Variety of miRNA Expression Profiles in the Developing and Mature CNS by Marika Kapsimali.- Interactions Between microRNAs and Transcription Factors in the Development and Function of the Nervous System by David J. Simon.- A microRNA Feedback Circuit in Midbrain Dopamine Neurons by Asa Abeliovich.- Fine-Tuning mRNA Translation at Synapses with microRNAs by Gerhard M. Schratt.- Neuronal P-bodies and Transport of microRNA-Repressed mRNAs by Florence Rage.- Crosstalk between microRNA and Epigenetic Regulation in Stem Cells by Keith Szulwach, Shuang Chang and Peng Jin.- microRNAs in CNS Development and Neurodegeneration: Insights from Drosophila Genetics by Stephen M. Cohen.- Drosophila as a Model for Neurodegenerative Disease: Roles of RNA Pathways in Pathogenesis by Nancy M. Bonini.- MicroRNAs in Sporadic Alzheimer’s Disease and Related Dementias by Sébastien S. Hébert, Wim Mandemakers, Aikaterini S. Papadopoulou and Bart De Strooper.- microRNA Dysregulation in Psychiatric Disorders by Bin Xu, Joseph A. Gogos and Maria Karayiorgou.- Subject Index.

Blurb

The discovery of microRNAs has revealed an unexpected and spectacular additional level of fine tuning of the genome and how genes are used again and again in different combinations to generate the complexity that underlies for instance the brain. Since the initial studies performed in C.elegans, we have gone a far way to begin to understand how microRNA pathways can have an impact on health and disease in human. Although microRNAs are abundantly expressed in the brain, relatively little is known about the multiple functions of these RNA molecules in the nervous system. Nevertheless, we know already that microRNA pathways play major roles in the proliferation, differentiation, function and maintenance of neuronal cells. Several intriguing studies have linked microRNAs as major regulators of the neuronal phenotype, and have implicated specific microRNAs in the regulation of synapse formation and plasticity. Dysfunction of microRNA pathways is also slowly emerging as a potential important contributor to the pathogenesis of major neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. These novel insights appear to be particular promising for the understanding of the very frequent and badly understood sporadic forms of these diseases as compared to the genetic forms. Thus, the better understanding of the implications of this novel field of molecular biology is crucial for the broad area of neurosciences, from the fundamental aspects to the clinic, and from novel diagnostic to potentially therapeutic applications for severe neurological and maybe psychiatric diseases.