Nora Bizzozero - Academia.edu (original) (raw)

Papers by Nora Bizzozero

Research paper thumbnail of Characterization of cross-tissue genetic-epigenetic effects and their patterns in schizophrenia

Genome medicine, Feb 26, 2018

One of the major challenges in current psychiatric epigenetic studies is the tissue specificity o... more One of the major challenges in current psychiatric epigenetic studies is the tissue specificity of epigenetic changes since access to brain samples is limited. Peripheral tissues have been studied as surrogates but the knowledge of cross-tissue genetic-epigenetic characteristics remains largely unknown. In this work, we conducted a comprehensive investigation of genetic influence on DNA methylation across brain and peripheral tissues with the aim to characterize cross-tissue genetic-epigenetic effects and their roles in the pathophysiology of psychiatric disorders. Genome-wide methylation quantitative trait loci (meQTLs) from brain prefrontal cortex, whole blood, and saliva were identified separately and compared. Focusing on cis-acting effects, we tested the enrichment of cross-tissue meQTLs among cross-tissue expression QTLs and genetic risk loci of various diseases, including major psychiatric disorders. CpGs targeted by cross-tissue meQTLs were also tested for genomic distributi...

Research paper thumbnail of Characterization of cross-tissue genetic-epigenetic effects and their patterns in schizophrenia

Genome medicine, Feb 26, 2018

One of the major challenges in current psychiatric epigenetic studies is the tissue specificity o... more One of the major challenges in current psychiatric epigenetic studies is the tissue specificity of epigenetic changes since access to brain samples is limited. Peripheral tissues have been studied as surrogates but the knowledge of cross-tissue genetic-epigenetic characteristics remains largely unknown. In this work, we conducted a comprehensive investigation of genetic influence on DNA methylation across brain and peripheral tissues with the aim to characterize cross-tissue genetic-epigenetic effects and their roles in the pathophysiology of psychiatric disorders. Genome-wide methylation quantitative trait loci (meQTLs) from brain prefrontal cortex, whole blood, and saliva were identified separately and compared. Focusing on cis-acting effects, we tested the enrichment of cross-tissue meQTLs among cross-tissue expression QTLs and genetic risk loci of various diseases, including major psychiatric disorders. CpGs targeted by cross-tissue meQTLs were also tested for genomic distributi...

Research paper thumbnail of Genetic markers of white matter integrity in schizophrenia revealed by parallel ICA

Frontiers in Human Neuroscience, 2015

Research paper thumbnail of Multimodal Neuroimaging in Schizophrenia: Description and Dissemination

Neuroinformatics

In this paper we describe an open-access collection of multimodal neuroimaging data in schizophre... more In this paper we describe an open-access collection of multimodal neuroimaging data in schizophrenia for release to the community. Data were acquired from approximately 100 patients with schizophrenia and 100 age-matched controls during rest as well as several task activation paradigms targeting a hierarchy of cognitive constructs. Neuroimaging data include structural MRI, functional MRI, diffusion MRI, MR spectroscopic imaging, and magnetoencephalography. For three of the hypothesis-driven projects, task activation paradigms were acquired on subsets of~200 volunteers which examined a range of sensory and cognitive processes (e.g., auditory sensory gating, auditory/visual multisensory integration, visual transverse patterning). Neuropsychological data were also acquired and genetic material via saliva samples were collected from most of the participants and have been typed for both genome-wide polymorphism data as well as genome-wide methylation data. Some results are also presented from the individual studies as well as from our data-driven multimodal analyses (e.g., multimodal examinations of network structure and network dynamics and multitask fMRI data analysis across projects). All data will be released through the Mind Research Network's collaborative informatics and neuroimaging suite (COINS).

Research paper thumbnail of Intra-axonal translation of Khsrp mRNA slows axon regeneration by destabilizing localized mRNAs

ABSTRACTProteins generated by localized mRNA translation in axons support nerve regeneration thro... more ABSTRACTProteins generated by localized mRNA translation in axons support nerve regeneration through retrograde injury signaling and localized axon growth mechanisms. RNA binding proteins (RBP) are needed for this and other aspects of post-transcriptional control of localized mRNAs, but only a limited number of axonal RBPs have been reported. We used a targeted mass spectrometry approach to profile the axonal RBPs in naïve, injured and regenerating PNS axons. We detected 76 axonal proteins that are reported to have RNA binding activity, with the levels of several of these axonal RBPs changing with axonal injury and regeneration. These axonal RBPs with altered axoplasm levels include KHSRP that we previously reported decreases neurite outgrowth in developing CNS neurons. We show that KHSRP levels rapidly increase in sciatic nerve axons after crush injury and remain elevated increasing in levels out to 28 days post-sciatic nerve crush injury. Khsrp mRNA localizes into axons and the ra...

Research paper thumbnail of Network modules linking expression and methylation in prefrontal cortex of schizophrenia

Epigenetics

Tremendous work has demonstrated the critical roles of genetics, epigenetics as well as their int... more Tremendous work has demonstrated the critical roles of genetics, epigenetics as well as their interplay in brain transcriptional regulations in the pathology of schizophrenia (SZ). There is great success currently in the dissection of the genetic components underlying risk-conferring transcriptomic networks. However, the study of regulating effect of epigenetics in the etiopathogenesis of SZ still faces many challenges. In this work, we investigated DNA methylation and gene expression from the dorsolateral prefrontal cortex (DLPFC) region of schizophrenia patients and healthy controls using weighted correlation network approach. We identified and replicated two expression and two methylation modules significantly associated with SZ. Among them, one pair of expression and methylation modules were significantly overlapped in the module genes which were significantly enriched in astrocyte-associated functional pathways, and specifically expressed in astrocytes. Another two linked expression-methylation module pairs were involved ageing process with module genes mostly related to oligodendrocyte development and myelination, and specifically expressed in oligodendrocytes. Further examination of underlying quantitative trait loci (QTLs) showed significant enrichment in genetic risk of most psychiatric disorders for expression QTLs but not for methylation QTLs. These results support the coherence between methylation and gene expression at the network level, and suggest a combinatorial effect of genetics and epigenetics in regulating gene expression networks specific to glia cells in relation to SZ and ageing process.

Research paper thumbnail of HuD Binds to and Regulates Circular RNAs Derived From Neuronal Development- and Synaptic Plasticity-Associated Genes

Research paper thumbnail of Abstract A64: Cold-inducible RNA binding protein (CIRP) links inflammation and breast cancer

Research paper thumbnail of A psychiatric disease-related circular RNA controls synaptic gene expression and cognition

Molecular Psychiatry

Although circular RNAs (circRNAs) are enriched in the mammalian brain, very little is known about... more Although circular RNAs (circRNAs) are enriched in the mammalian brain, very little is known about their potential involvement in brain function and psychiatric disease. Here, we show that circHomer1a, a neuronal-enriched circRNA abundantly expressed in the frontal cortex, derived from Homer protein homolog 1 (HOMER1), is significantly reduced in both the prefrontal cortex (PFC) and induced pluripotent stem cell-derived neuronal cultures from patients with schizophrenia (SCZ) and bipolar disorder (BD). Moreover, alterations in circHomer1a were positively associated with the age of onset of SCZ in both the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). No correlations between the age of onset of SCZ and linear HOMER1 mRNA were observed, whose expression was mostly unaltered in BD and SCZ postmortem brain. Using in vivo circRNA-specific knockdown of circHomer1a in mouse PFC, we show that it modulates the expression of numerous alternative mRNA transcripts from g...

Research paper thumbnail of 171. Combined Neuropathological, Genetic and Imaging Approaches Reveal Myelination Abnormalities in Schizophrenia

Research paper thumbnail of F163. A Psychiatric Disease-Related Circular RNA Controls Neuronal Function and Cognition

Research paper thumbnail of CHARACTERIZATION OF CROSS-TISSUE mQTL EFFECTS AND THEIR RELEVANCE IN PSYCHIATRIC DISORDERS

European Neuropsychopharmacology

Research paper thumbnail of Dysregulated In Psychiatric Disorders Circular RNAs Interact With Rna Binding Proteins To Regulate Synaptic Plasticity

European Neuropsychopharmacology

Research paper thumbnail of Neuropsychiatric Implications Of RNA-Binding Proteins HuD And KSRP Revealed By Genome-Wide Identification Of Their Targets

European Neuropsychopharmacology

Research paper thumbnail of Network modules linking expression and methylation in prefrontal cortex of schizophrenia

Tremendous work has demonstrated the critical roles of genetics, epigenetics as well as their int... more Tremendous work has demonstrated the critical roles of genetics, epigenetics as well as their interplay in brain transcriptional regulations in the pathology of schizophrenia (SCZ). There is great success currently in the dissection of the genetic components underlying risk-conferring transcriptomic networks. However, the study of regulating effect of epigenetics, as a modulator of environmental factors, in the etiopathogenesis of SCZ still faces many challenges. In this work we investigated DNA methylation and gene expression from the dorsolateral prefrontal cortex (DLPFC) region of schizophrenia patients and healthy controls using weighted correlation network approaches. We identified and replicated two expression and two methylation modules significantly associated with SCZ. Among them, one pair of expression and methylation modules were significantly overlapped in the module genes which were enriched in astrocyte-associated functional pathways, and specifically expressed in astr...

Research paper thumbnail of A Perspective of the Cross-Tissue Interplay of Genetics, Epigenetics, and Transcriptomics, and Their Relation to Brain Based Phenotypes in Schizophrenia

Frontiers in genetics, 2018

Genetic association studies of psychiatric disorders have provided unprecedented insight into dis... more Genetic association studies of psychiatric disorders have provided unprecedented insight into disease risk profiles with high confidence. Yet, the next research challenge is how to translate this rich information into mechanisms of disease, and further help interventions and treatments. Given other comprehensive reviews elsewhere, here we want to discuss the research approaches that integrate information across various tissue types. Taking schizophrenia as an example, the tissues, cells, or organisms being investigated include postmortem brain tissues or neurons, peripheral blood and saliva, brain imaging, and cell lines, particularly human induced pluripotent stem cells (iPSC) and iPSC derived neurons. There is a wealth of information on the molecular signatures including genetics, epigenetics, and transcriptomics of various tissues, along with neuronal phenotypic measurements including neuronal morphometry and function, together with brain imaging and other techniques that provide...

Research paper thumbnail of Axonal mRNA transport and translation at a glance

Journal of cell science, Jan 13, 2018

Localization and translation of mRNAs within different subcellular domains provides an important ... more Localization and translation of mRNAs within different subcellular domains provides an important mechanism to spatially and temporally introduce new proteins in polarized cells. Neurons make use of this localized protein synthesis during initial growth, regeneration and functional maintenance of their axons. Although the first evidence for protein synthesis in axons dates back to 1960s, improved methodologies, including the ability to isolate axons to purity, highly sensitive RNA detection methods and imaging approaches, have shed new light on the complexity of the transcriptome of the axon and how it is regulated. Moreover, these efforts are now uncovering new roles for locally synthesized proteins in neurological diseases and injury responses. In this Cell Science at a Glance article and the accompanying poster, we provide an overview of how axonal mRNA transport and translation are regulated, and discuss their emerging links to neurological disorders and neural repair.

Research paper thumbnail of MicroRNA132 associated multimodal neuroimaging patterns in unmedicated major depressive disorder

Brain : a journal of neurology, Jan 2, 2018

There is compelling evidence that epigenetic factors contribute to the manifestation of depressio... more There is compelling evidence that epigenetic factors contribute to the manifestation of depression, in which microRNA132 (miR-132) is suggested to play a pivotal role in the pathogenesis and neuronal mechanisms underlying the symptoms of depression. Additionally, several depression-associated genes [MECP2, ARHGAP32 (p250GAP), CREB, and period genes] were experimentally validated as miR-132 targets. However, most studies regarding miR-132 in major depressive disorder are based on post-mortem, animal models or genetic comparisons. This work will be the first attempt to investigate how miR-132 dysregulation may impact covariation of multimodal brain imaging data in 81 unmedicated major depressive patients and 123 demographically-matched healthy controls, as well as in a medication-naïve subset of major depressive patients. MiR-132 values in blood (patients > controls) was used as a prior reference to guide fusion of three MRI features: fractional amplitude of low frequency fluctuati...

Research paper thumbnail of Axonal localization of neuritin/CPG15 mRNA is limited by competition for HuD binding

Journal of cell science, Jan 4, 2017

HuD protein has been shown to stabilize mRNAs with AU-rich elements (ARE) in their 3'UTRs, in... more HuD protein has been shown to stabilize mRNAs with AU-rich elements (ARE) in their 3'UTRs, including Gap43 that has been linked to axon growth. HuD also binds to Neuritin (Nrn1), whose 3'UTR contains ARE sequences. Although Nrn1's 3'UTR was shown to have axonal localizing activity in embryonic hippocampal neurons, it was not active in adult DRG neurons. Here, we asked why the 3'UTR is not sufficient to localize Nrn1 mRNA into DRG axons. HuD overexpression increases the axonal localizing activity of Nrn1's 3'UTR in DRG. HuD binds directly to Nrn1's ARE with about two-fold higher affinity than Gap43's ARE. Though Nrn1 ARE can displace Gap43 ARE from HuD binding, HuD binds to the full 3'UTR of Gap43 with higher affinity such that higher levels of Nrn1 are needed to displace the 3'UTR. Localizing activity of Nrn1's 3'UTR increases when endogenous Gap43 is depleted from DRG neurons. Taken together, our data indicate that endogenous Nrn1...

Research paper thumbnail of Diverse roles of the nucleic acid-binding protein KHSRP in cell differentiation and disease

Wiley Interdisciplinary Reviews: RNA, 2015

The single-stranded nucleic acid-binding protein KHSRP (KH-type splicing regulatory protein) modu... more The single-stranded nucleic acid-binding protein KHSRP (KH-type splicing regulatory protein) modulates RNA life and gene expression at various levels. KHSRP controls important cellular functions as different as proliferation, differentiation, metabolism, and response to infectious agents. We summarize and discuss experimental evidence providing a potential link between changes in KHSRP expression/function and human diseases including neuromuscular disorders, obesity, type II diabetes, and cancer. For further resources related to this article, please visit the WIREs website.

Research paper thumbnail of Characterization of cross-tissue genetic-epigenetic effects and their patterns in schizophrenia

Genome medicine, Feb 26, 2018

One of the major challenges in current psychiatric epigenetic studies is the tissue specificity o... more One of the major challenges in current psychiatric epigenetic studies is the tissue specificity of epigenetic changes since access to brain samples is limited. Peripheral tissues have been studied as surrogates but the knowledge of cross-tissue genetic-epigenetic characteristics remains largely unknown. In this work, we conducted a comprehensive investigation of genetic influence on DNA methylation across brain and peripheral tissues with the aim to characterize cross-tissue genetic-epigenetic effects and their roles in the pathophysiology of psychiatric disorders. Genome-wide methylation quantitative trait loci (meQTLs) from brain prefrontal cortex, whole blood, and saliva were identified separately and compared. Focusing on cis-acting effects, we tested the enrichment of cross-tissue meQTLs among cross-tissue expression QTLs and genetic risk loci of various diseases, including major psychiatric disorders. CpGs targeted by cross-tissue meQTLs were also tested for genomic distributi...

Research paper thumbnail of Characterization of cross-tissue genetic-epigenetic effects and their patterns in schizophrenia

Genome medicine, Feb 26, 2018

One of the major challenges in current psychiatric epigenetic studies is the tissue specificity o... more One of the major challenges in current psychiatric epigenetic studies is the tissue specificity of epigenetic changes since access to brain samples is limited. Peripheral tissues have been studied as surrogates but the knowledge of cross-tissue genetic-epigenetic characteristics remains largely unknown. In this work, we conducted a comprehensive investigation of genetic influence on DNA methylation across brain and peripheral tissues with the aim to characterize cross-tissue genetic-epigenetic effects and their roles in the pathophysiology of psychiatric disorders. Genome-wide methylation quantitative trait loci (meQTLs) from brain prefrontal cortex, whole blood, and saliva were identified separately and compared. Focusing on cis-acting effects, we tested the enrichment of cross-tissue meQTLs among cross-tissue expression QTLs and genetic risk loci of various diseases, including major psychiatric disorders. CpGs targeted by cross-tissue meQTLs were also tested for genomic distributi...

Research paper thumbnail of Genetic markers of white matter integrity in schizophrenia revealed by parallel ICA

Frontiers in Human Neuroscience, 2015

Research paper thumbnail of Multimodal Neuroimaging in Schizophrenia: Description and Dissemination

Neuroinformatics

In this paper we describe an open-access collection of multimodal neuroimaging data in schizophre... more In this paper we describe an open-access collection of multimodal neuroimaging data in schizophrenia for release to the community. Data were acquired from approximately 100 patients with schizophrenia and 100 age-matched controls during rest as well as several task activation paradigms targeting a hierarchy of cognitive constructs. Neuroimaging data include structural MRI, functional MRI, diffusion MRI, MR spectroscopic imaging, and magnetoencephalography. For three of the hypothesis-driven projects, task activation paradigms were acquired on subsets of~200 volunteers which examined a range of sensory and cognitive processes (e.g., auditory sensory gating, auditory/visual multisensory integration, visual transverse patterning). Neuropsychological data were also acquired and genetic material via saliva samples were collected from most of the participants and have been typed for both genome-wide polymorphism data as well as genome-wide methylation data. Some results are also presented from the individual studies as well as from our data-driven multimodal analyses (e.g., multimodal examinations of network structure and network dynamics and multitask fMRI data analysis across projects). All data will be released through the Mind Research Network's collaborative informatics and neuroimaging suite (COINS).

Research paper thumbnail of Intra-axonal translation of Khsrp mRNA slows axon regeneration by destabilizing localized mRNAs

ABSTRACTProteins generated by localized mRNA translation in axons support nerve regeneration thro... more ABSTRACTProteins generated by localized mRNA translation in axons support nerve regeneration through retrograde injury signaling and localized axon growth mechanisms. RNA binding proteins (RBP) are needed for this and other aspects of post-transcriptional control of localized mRNAs, but only a limited number of axonal RBPs have been reported. We used a targeted mass spectrometry approach to profile the axonal RBPs in naïve, injured and regenerating PNS axons. We detected 76 axonal proteins that are reported to have RNA binding activity, with the levels of several of these axonal RBPs changing with axonal injury and regeneration. These axonal RBPs with altered axoplasm levels include KHSRP that we previously reported decreases neurite outgrowth in developing CNS neurons. We show that KHSRP levels rapidly increase in sciatic nerve axons after crush injury and remain elevated increasing in levels out to 28 days post-sciatic nerve crush injury. Khsrp mRNA localizes into axons and the ra...

Research paper thumbnail of Network modules linking expression and methylation in prefrontal cortex of schizophrenia

Epigenetics

Tremendous work has demonstrated the critical roles of genetics, epigenetics as well as their int... more Tremendous work has demonstrated the critical roles of genetics, epigenetics as well as their interplay in brain transcriptional regulations in the pathology of schizophrenia (SZ). There is great success currently in the dissection of the genetic components underlying risk-conferring transcriptomic networks. However, the study of regulating effect of epigenetics in the etiopathogenesis of SZ still faces many challenges. In this work, we investigated DNA methylation and gene expression from the dorsolateral prefrontal cortex (DLPFC) region of schizophrenia patients and healthy controls using weighted correlation network approach. We identified and replicated two expression and two methylation modules significantly associated with SZ. Among them, one pair of expression and methylation modules were significantly overlapped in the module genes which were significantly enriched in astrocyte-associated functional pathways, and specifically expressed in astrocytes. Another two linked expression-methylation module pairs were involved ageing process with module genes mostly related to oligodendrocyte development and myelination, and specifically expressed in oligodendrocytes. Further examination of underlying quantitative trait loci (QTLs) showed significant enrichment in genetic risk of most psychiatric disorders for expression QTLs but not for methylation QTLs. These results support the coherence between methylation and gene expression at the network level, and suggest a combinatorial effect of genetics and epigenetics in regulating gene expression networks specific to glia cells in relation to SZ and ageing process.

Research paper thumbnail of HuD Binds to and Regulates Circular RNAs Derived From Neuronal Development- and Synaptic Plasticity-Associated Genes

Research paper thumbnail of Abstract A64: Cold-inducible RNA binding protein (CIRP) links inflammation and breast cancer

Research paper thumbnail of A psychiatric disease-related circular RNA controls synaptic gene expression and cognition

Molecular Psychiatry

Although circular RNAs (circRNAs) are enriched in the mammalian brain, very little is known about... more Although circular RNAs (circRNAs) are enriched in the mammalian brain, very little is known about their potential involvement in brain function and psychiatric disease. Here, we show that circHomer1a, a neuronal-enriched circRNA abundantly expressed in the frontal cortex, derived from Homer protein homolog 1 (HOMER1), is significantly reduced in both the prefrontal cortex (PFC) and induced pluripotent stem cell-derived neuronal cultures from patients with schizophrenia (SCZ) and bipolar disorder (BD). Moreover, alterations in circHomer1a were positively associated with the age of onset of SCZ in both the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). No correlations between the age of onset of SCZ and linear HOMER1 mRNA were observed, whose expression was mostly unaltered in BD and SCZ postmortem brain. Using in vivo circRNA-specific knockdown of circHomer1a in mouse PFC, we show that it modulates the expression of numerous alternative mRNA transcripts from g...

Research paper thumbnail of 171. Combined Neuropathological, Genetic and Imaging Approaches Reveal Myelination Abnormalities in Schizophrenia

Research paper thumbnail of F163. A Psychiatric Disease-Related Circular RNA Controls Neuronal Function and Cognition

Research paper thumbnail of CHARACTERIZATION OF CROSS-TISSUE mQTL EFFECTS AND THEIR RELEVANCE IN PSYCHIATRIC DISORDERS

European Neuropsychopharmacology

Research paper thumbnail of Dysregulated In Psychiatric Disorders Circular RNAs Interact With Rna Binding Proteins To Regulate Synaptic Plasticity

European Neuropsychopharmacology

Research paper thumbnail of Neuropsychiatric Implications Of RNA-Binding Proteins HuD And KSRP Revealed By Genome-Wide Identification Of Their Targets

European Neuropsychopharmacology

Research paper thumbnail of Network modules linking expression and methylation in prefrontal cortex of schizophrenia

Tremendous work has demonstrated the critical roles of genetics, epigenetics as well as their int... more Tremendous work has demonstrated the critical roles of genetics, epigenetics as well as their interplay in brain transcriptional regulations in the pathology of schizophrenia (SCZ). There is great success currently in the dissection of the genetic components underlying risk-conferring transcriptomic networks. However, the study of regulating effect of epigenetics, as a modulator of environmental factors, in the etiopathogenesis of SCZ still faces many challenges. In this work we investigated DNA methylation and gene expression from the dorsolateral prefrontal cortex (DLPFC) region of schizophrenia patients and healthy controls using weighted correlation network approaches. We identified and replicated two expression and two methylation modules significantly associated with SCZ. Among them, one pair of expression and methylation modules were significantly overlapped in the module genes which were enriched in astrocyte-associated functional pathways, and specifically expressed in astr...

Research paper thumbnail of A Perspective of the Cross-Tissue Interplay of Genetics, Epigenetics, and Transcriptomics, and Their Relation to Brain Based Phenotypes in Schizophrenia

Frontiers in genetics, 2018

Genetic association studies of psychiatric disorders have provided unprecedented insight into dis... more Genetic association studies of psychiatric disorders have provided unprecedented insight into disease risk profiles with high confidence. Yet, the next research challenge is how to translate this rich information into mechanisms of disease, and further help interventions and treatments. Given other comprehensive reviews elsewhere, here we want to discuss the research approaches that integrate information across various tissue types. Taking schizophrenia as an example, the tissues, cells, or organisms being investigated include postmortem brain tissues or neurons, peripheral blood and saliva, brain imaging, and cell lines, particularly human induced pluripotent stem cells (iPSC) and iPSC derived neurons. There is a wealth of information on the molecular signatures including genetics, epigenetics, and transcriptomics of various tissues, along with neuronal phenotypic measurements including neuronal morphometry and function, together with brain imaging and other techniques that provide...

Research paper thumbnail of Axonal mRNA transport and translation at a glance

Journal of cell science, Jan 13, 2018

Localization and translation of mRNAs within different subcellular domains provides an important ... more Localization and translation of mRNAs within different subcellular domains provides an important mechanism to spatially and temporally introduce new proteins in polarized cells. Neurons make use of this localized protein synthesis during initial growth, regeneration and functional maintenance of their axons. Although the first evidence for protein synthesis in axons dates back to 1960s, improved methodologies, including the ability to isolate axons to purity, highly sensitive RNA detection methods and imaging approaches, have shed new light on the complexity of the transcriptome of the axon and how it is regulated. Moreover, these efforts are now uncovering new roles for locally synthesized proteins in neurological diseases and injury responses. In this Cell Science at a Glance article and the accompanying poster, we provide an overview of how axonal mRNA transport and translation are regulated, and discuss their emerging links to neurological disorders and neural repair.

Research paper thumbnail of MicroRNA132 associated multimodal neuroimaging patterns in unmedicated major depressive disorder

Brain : a journal of neurology, Jan 2, 2018

There is compelling evidence that epigenetic factors contribute to the manifestation of depressio... more There is compelling evidence that epigenetic factors contribute to the manifestation of depression, in which microRNA132 (miR-132) is suggested to play a pivotal role in the pathogenesis and neuronal mechanisms underlying the symptoms of depression. Additionally, several depression-associated genes [MECP2, ARHGAP32 (p250GAP), CREB, and period genes] were experimentally validated as miR-132 targets. However, most studies regarding miR-132 in major depressive disorder are based on post-mortem, animal models or genetic comparisons. This work will be the first attempt to investigate how miR-132 dysregulation may impact covariation of multimodal brain imaging data in 81 unmedicated major depressive patients and 123 demographically-matched healthy controls, as well as in a medication-naïve subset of major depressive patients. MiR-132 values in blood (patients > controls) was used as a prior reference to guide fusion of three MRI features: fractional amplitude of low frequency fluctuati...

Research paper thumbnail of Axonal localization of neuritin/CPG15 mRNA is limited by competition for HuD binding

Journal of cell science, Jan 4, 2017

HuD protein has been shown to stabilize mRNAs with AU-rich elements (ARE) in their 3'UTRs, in... more HuD protein has been shown to stabilize mRNAs with AU-rich elements (ARE) in their 3'UTRs, including Gap43 that has been linked to axon growth. HuD also binds to Neuritin (Nrn1), whose 3'UTR contains ARE sequences. Although Nrn1's 3'UTR was shown to have axonal localizing activity in embryonic hippocampal neurons, it was not active in adult DRG neurons. Here, we asked why the 3'UTR is not sufficient to localize Nrn1 mRNA into DRG axons. HuD overexpression increases the axonal localizing activity of Nrn1's 3'UTR in DRG. HuD binds directly to Nrn1's ARE with about two-fold higher affinity than Gap43's ARE. Though Nrn1 ARE can displace Gap43 ARE from HuD binding, HuD binds to the full 3'UTR of Gap43 with higher affinity such that higher levels of Nrn1 are needed to displace the 3'UTR. Localizing activity of Nrn1's 3'UTR increases when endogenous Gap43 is depleted from DRG neurons. Taken together, our data indicate that endogenous Nrn1...

Research paper thumbnail of Diverse roles of the nucleic acid-binding protein KHSRP in cell differentiation and disease

Wiley Interdisciplinary Reviews: RNA, 2015

The single-stranded nucleic acid-binding protein KHSRP (KH-type splicing regulatory protein) modu... more The single-stranded nucleic acid-binding protein KHSRP (KH-type splicing regulatory protein) modulates RNA life and gene expression at various levels. KHSRP controls important cellular functions as different as proliferation, differentiation, metabolism, and response to infectious agents. We summarize and discuss experimental evidence providing a potential link between changes in KHSRP expression/function and human diseases including neuromuscular disorders, obesity, type II diabetes, and cancer. For further resources related to this article, please visit the WIREs website.