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Article ; Online: Reply to: Potential contribution of PEP carboxykinase-dependent malate dismutation to the hypoxia response in C. elegans.

Vora, Mehul / Pyonteck, Stephanie M / Popovitchenko, Tatiana / Matlack, Tarmie L / Prashar, Aparna / Kane, Nanci S / Favate, John / Shah, Premal / Rongo, Christopher

Nature communications

2023 Volume 14, Issue 1, Page(s) 3937

MeSH term(s)	Animals ; Caenorhabditis elegans/metabolism ; Malates ; Phosphoenolpyruvate Carboxykinase (GTP)/metabolism ; Photosynthesis
Chemical Substances	malic acid (817L1N4CKP) ; Malates ; Phosphoenolpyruvate Carboxykinase (GTP) (EC 4.1.1.32)
Language	English
Publishing date	2023-07-04
Publishing country	England
Document type	Letter ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-39511-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Transcriptional and Post-Transcriptional Mechanisms of the Development of Neocortical Lamination.

Popovitchenko, Tatiana / Rasin, Mladen-Roko

Frontiers in neuroanatomy

2017 Volume 11, Page(s) 102

Abstract: The neocortex is a laminated brain structure that is the seat of higher cognitive capacity and responses, long-term memory, sensory and emotional functions, and voluntary motor behavior. Proper lamination requires that progenitor cells give rise to a ... ...

Abstract	The neocortex is a laminated brain structure that is the seat of higher cognitive capacity and responses, long-term memory, sensory and emotional functions, and voluntary motor behavior. Proper lamination requires that progenitor cells give rise to a neuron, that the immature neuron can migrate away from its mother cell and past other cells, and finally that the immature neuron can take its place and adopt a mature identity characterized by connectivity and gene expression; thus lamination proceeds through three steps: genesis, migration, and maturation. Each neocortical layer contains pyramidal neurons that share specific morphological and molecular characteristics that stem from their prenatal birth date. Transcription factors are dynamic proteins because of the cohort of downstream factors that they regulate. RNA-binding proteins are no less dynamic, and play important roles in every step of mRNA processing. Indeed, recent screens have uncovered post-transcriptional mechanisms as being integral regulatory mechanisms to neocortical development. Here, we summarize major aspects of neocortical laminar development, emphasizing transcriptional and post-transcriptional mechanisms, with the aim of spurring increased understanding and study of its intricacies.
Language	English
Publishing date	2017-11-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452969-2
ISSN	1662-5129
ISSN	1662-5129
DOI	10.3389/fnana.2017.00102
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Article ; Online: The hypoxia response pathway promotes PEP carboxykinase and gluconeogenesis in C. elegans.

Vora, Mehul / Pyonteck, Stephanie M / Popovitchenko, Tatiana / Matlack, Tarmie L / Prashar, Aparna / Kane, Nanci S / Favate, John / Shah, Premal / Rongo, Christopher

Nature communications

2022 Volume 13, Issue 1, Page(s) 6168

Abstract: Actively dividing cells, including some cancers, rely on aerobic glycolysis rather than oxidative phosphorylation to generate energy, a phenomenon termed the Warburg effect. Constitutive activation of the Hypoxia Inducible Factor (HIF-1), a transcription ...

Abstract	Actively dividing cells, including some cancers, rely on aerobic glycolysis rather than oxidative phosphorylation to generate energy, a phenomenon termed the Warburg effect. Constitutive activation of the Hypoxia Inducible Factor (HIF-1), a transcription factor known for mediating an adaptive response to oxygen deprivation (hypoxia), is a hallmark of the Warburg effect. HIF-1 is thought to promote glycolysis and suppress oxidative phosphorylation. Here, we instead show that HIF-1 can promote gluconeogenesis. Using a multiomics approach, we reveal the genomic, transcriptomic, and metabolomic landscapes regulated by constitutively active HIF-1 in C. elegans. We use RNA-seq and ChIP-seq under aerobic conditions to analyze mutants lacking EGL-9, a key negative regulator of HIF-1. We integrate these approaches to identify over two hundred genes directly and functionally upregulated by HIF-1, including the PEP carboxykinase PCK-1, a rate-limiting mediator of gluconeogenesis. This activation of PCK-1 by HIF-1 promotes survival in response to both oxidative and hypoxic stress. Our work identifies functional direct targets of HIF-1 in vivo, comprehensively describing the metabolome induced by HIF-1 activation in an organism.
MeSH term(s)	Animals ; Caenorhabditis elegans/genetics ; Gluconeogenesis/genetics ; Transcription Factors/genetics ; Cell Hypoxia ; Hypoxia/genetics ; Oxygen ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics
Chemical Substances	Transcription Factors ; Oxygen (S88TT14065) ; Hypoxia-Inducible Factor 1, alpha Subunit
Language	English
Publishing date	2022-10-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-33849-x
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Article ; Online: Reply to

Mehul Vora / Stephanie M. Pyonteck / Tatiana Popovitchenko / Tarmie L. Matlack / Aparna Prashar / Nanci S. Kane / John Favate / Premal Shah / Christopher Rongo

Nature Communications, Vol 14, Iss 1, Pp 1-

Potential contribution of PEP carboxykinase-dependent malate dismutation to the hypoxia response in C. elegans

2023 Volume 4

Keywords	Science ; Q
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The frontier of RNA metamorphosis and ribosome signature in neocortical development.

Kraushar, Matthew L / Popovitchenko, Tatiana / Volk, Nicole L / Rasin, Mladen-Roko

International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience

2016 Volume 55, Page(s) 131–139

Abstract: More than a passive effector of gene expression, mRNA translation (protein synthesis) by the ribosome is a rapidly tunable and dynamic molecular mechanism. Neurodevelopmental disorders are associated with abnormalities in mRNA translation, protein ... ...

Abstract	More than a passive effector of gene expression, mRNA translation (protein synthesis) by the ribosome is a rapidly tunable and dynamic molecular mechanism. Neurodevelopmental disorders are associated with abnormalities in mRNA translation, protein synthesis, and neocortical development; yet, we know little about the molecular mechanisms underlying these abnormalities. Furthermore, our understanding of regulation of the ribosome and mRNA translation during normal brain development is only in its early stages. mRNA translation is emerging as a key driver of the rapid and timed regulation of spatiotemporal gene expression in the developing nervous system, including the neocortex. In this review, we focus on the regulatory role of the ribosome in neocortical development, and construct a current understanding of how ribosomal complex specificity may contribute to the development of the neocortex. We also present a microarray analysis of ribosomal protein-coding mRNAs across the neurogenic phase of neocortical development, in addition to the dynamic enrichment of these mRNAs in actively translating neocortical polysomal ribosomes. Understanding the multivariate control of mRNA translation by ribosomal complex specificity will be critical to reveal the intricate mechanisms of normal brain development and pathologies of neurodevelopmental disorders.
MeSH term(s)	Animals ; Gene Expression Profiling ; Humans ; Metamorphosis, Biological/genetics ; Neocortex/growth & development ; RNA, Messenger/metabolism ; Ribosomes/genetics
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2016-05-27
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	605533-3
ISSN	1873-474X ; 0736-5748
ISSN (online)	1873-474X
ISSN	0736-5748
DOI	10.1016/j.ijdevneu.2016.02.003
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Article ; Online: The hypoxia response pathway promotes PEP carboxykinase and gluconeogenesis in C. elegans

Mehul Vora / Stephanie M. Pyonteck / Tatiana Popovitchenko / Tarmie L. Matlack / Aparna Prashar / Nanci S. Kane / John Favate / Premal Shah / Christopher Rongo

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 15

Abstract: Abstract Actively dividing cells, including some cancers, rely on aerobic glycolysis rather than oxidative phosphorylation to generate energy, a phenomenon termed the Warburg effect. Constitutive activation of the Hypoxia Inducible Factor (HIF-1), a ... ...

Abstract	Abstract Actively dividing cells, including some cancers, rely on aerobic glycolysis rather than oxidative phosphorylation to generate energy, a phenomenon termed the Warburg effect. Constitutive activation of the Hypoxia Inducible Factor (HIF-1), a transcription factor known for mediating an adaptive response to oxygen deprivation (hypoxia), is a hallmark of the Warburg effect. HIF-1 is thought to promote glycolysis and suppress oxidative phosphorylation. Here, we instead show that HIF-1 can promote gluconeogenesis. Using a multiomics approach, we reveal the genomic, transcriptomic, and metabolomic landscapes regulated by constitutively active HIF-1 in C. elegans. We use RNA-seq and ChIP-seq under aerobic conditions to analyze mutants lacking EGL-9, a key negative regulator of HIF-1. We integrate these approaches to identify over two hundred genes directly and functionally upregulated by HIF-1, including the PEP carboxykinase PCK-1, a rate-limiting mediator of gluconeogenesis. This activation of PCK-1 by HIF-1 promotes survival in response to both oxidative and hypoxic stress. Our work identifies functional direct targets of HIF-1 in vivo, comprehensively describing the metabolome induced by HIF-1 activation in an organism.
Keywords	Science ; Q
Subject code	610
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans.

Doitsidou, Maria / Flames, Nuria / Topalidou, Irini / Abe, Namiko / Felton, Terry / Remesal, Laura / Popovitchenko, Tatiana / Mann, Richard / Chalfie, Martin / Hobert, Oliver

Genes & development

2013 Volume 27, Issue 12, Page(s) 1391–1405

Abstract: Terminal differentiation programs in the nervous system are encoded by cis-regulatory elements that control the expression of terminal features of individual neuron types. We decoded the regulatory information that controls the expression of five enzymes ...

Abstract	Terminal differentiation programs in the nervous system are encoded by cis-regulatory elements that control the expression of terminal features of individual neuron types. We decoded the regulatory information that controls the expression of five enzymes and transporters that define the terminal identity of all eight dopaminergic neurons in the nervous system of the Caenorhabditis elegans hermaphrodite. We show that the tightly coordinated, robust expression of these dopaminergic enzymes and transporters ("dopamine pathway") is ensured through a combinatorial cis-regulatory signature that is shared by all dopamine pathway genes. This signature is composed of an Ets domain-binding site, recognized by the previously described AST-1 Ets domain factor, and two distinct types of homeodomain-binding sites that act in a partially redundant manner. Through genetic screens, we identified the sole C. elegans Distalless/Dlx ortholog, ceh-43, as a factor that acts through one of the homeodomain sites to control both induction and maintenance of terminal dopaminergic fate. The second type of homeodomain site is a Pbx-type site, which is recognized in a partially redundant and neuron subtype-specific manner by two Pbx factors, ceh-20 and ceh-40, revealing novel roles of Pbx factors in the context of terminal neuron differentiation. Taken together, we revealed a specific regulatory signature and cognate, terminal selector-type transcription factors that define the entire dopaminergic nervous system of an animal. Dopaminergic neurons in the mouse olfactory bulb express a similar combinatorial transcription factor collective of Ets/Dlx/Pbx factors, suggesting deep phylogenetic conservation of dopaminergic regulatory programs.
MeSH term(s)	Amino Acid Sequence ; Animals ; Caenorhabditis elegans/cytology ; Caenorhabditis elegans/embryology ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Cell Differentiation/genetics ; DNA Mutational Analysis ; Dopaminergic Neurons/cytology ; Dopaminergic Neurons/metabolism ; Gene Expression Regulation, Developmental ; Molecular Sequence Data ; Nervous System/cytology ; Nervous System/embryology ; Regulatory Elements, Transcriptional/genetics ; Sequence Alignment
Chemical Substances	Caenorhabditis elegans Proteins
Language	English
Publishing date	2013-06-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.217224.113
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Zs.MG 54: Show issues

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Article ; Online: Translational derepression of Elavl4 isoforms at their alternative 5' UTRs determines neuronal development.

Popovitchenko, Tatiana / Park, Yongkyu / Page, Nicholas F / Luo, Xiaobing / Krsnik, Zeljka / Liu, Yuan / Salamon, Iva / Stephenson, Jessica D / Kraushar, Matthew L / Volk, Nicole L / Patel, Sejal M / Wijeratne, H R Sagara / Li, Diana / Suthar, Kandarp S / Wach, Aaron / Sun, Miao / Arnold, Sebastian J / Akamatsu, Wado / Okano, Hideyuki /

Paillard, Luc / Zhang, Huaye / Buyske, Steven / Kostovic, Ivica / De Rubeis, Silvia / Hart, Ronald P / Rasin, Mladen-Roko

Nature communications

2020 Volume 11, Issue 1, Page(s) 1674

Abstract: Neurodevelopment requires precise regulation of gene expression, including post-transcriptional regulatory events such as alternative splicing and mRNA translation. However, translational regulation of specific isoforms during neurodevelopment and the ... ...

Abstract	Neurodevelopment requires precise regulation of gene expression, including post-transcriptional regulatory events such as alternative splicing and mRNA translation. However, translational regulation of specific isoforms during neurodevelopment and the mechanisms behind it remain unknown. Using RNA-seq analysis of mouse neocortical polysomes, here we report translationally repressed and derepressed mRNA isoforms during neocortical neurogenesis whose orthologs include risk genes for neurodevelopmental disorders. We demonstrate that the translation of distinct mRNA isoforms of the RNA binding protein (RBP), Elavl4, in radial glia progenitors and early neurons depends on its alternative 5' UTRs. Furthermore, 5' UTR-driven Elavl4 isoform-specific translation depends on upstream control by another RBP, Celf1. Celf1 regulation of Elavl4 translation dictates development of glutamatergic neurons. Our findings reveal a dynamic interplay between distinct RBPs and alternative 5' UTRs in neuronal development and underscore the risk of post-transcriptional dysregulation in co-occurring neurodevelopmental disorders.
MeSH term(s)	5' Untranslated Regions/genetics ; Alternative Splicing ; Animals ; CELF1 Protein/metabolism ; Cell Line, Tumor ; ELAV-Like Protein 4/genetics ; Female ; Gene Expression Regulation, Developmental ; Glutamic Acid/metabolism ; Male ; Mice ; Mice, Transgenic ; Neocortex/cytology ; Neocortex/growth & development ; Neural Stem Cells/metabolism ; Neurogenesis/genetics ; Neuroglia/metabolism ; Neurons/metabolism ; Polyribosomes/metabolism ; Primary Cell Culture ; Protein Biosynthesis/genetics ; RNA Isoforms/genetics ; RNA-Seq
Chemical Substances	5' Untranslated Regions ; CELF1 Protein ; CELF1 protein, mouse ; ELAV-Like Protein 4 ; Elavl4 protein, mouse ; RNA Isoforms ; Glutamic Acid (3KX376GY7L)
Language	English
Publishing date	2020-04-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-15412-8
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Article ; Online: Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development

Tatiana Popovitchenko / Yongkyu Park / Nicholas F. Page / Xiaobing Luo / Zeljka Krsnik / Yuan Liu / Iva Salamon / Jessica D. Stephenson / Matthew L. Kraushar / Nicole L. Volk / Sejal M. Patel / H. R. Sagara Wijeratne / Diana Li / Kandarp S. Suthar / Aaron Wach / Miao Sun / Sebastian J. Arnold / Wado Akamatsu / Hideyuki Okano /

Luc Paillard / Huaye Zhang / Steven Buyske / Ivica Kostovic / Silvia De Rubeis / Ronald P. Hart / Mladen-Roko Rasin

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 21

Abstract: Translational regulation of isoforms in the developing nervous system is not well understood. Here, the authors report translational de-repression of RNA binding protein isoforms at their 5′UTRs in the neocortex and show the neurodevelopmental risk of ... ...

Abstract	Translational regulation of isoforms in the developing nervous system is not well understood. Here, the authors report translational de-repression of RNA binding protein isoforms at their 5′UTRs in the neocortex and show the neurodevelopmental risk of post-transcriptional dysregulation.
Keywords	Science ; Q
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development

Luc Paillard / Huaye Zhang / Steven Buyske / Ivica Kostovic / Silvia De Rubeis / Ronald P. Hart / Mladen-Roko Rasin

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 21

Abstract	Translational regulation of isoforms in the developing nervous system is not well understood. Here, the authors report translational de-repression of RNA binding protein isoforms at their 5′UTRs in the neocortex and show the neurodevelopmental risk of post-transcriptional dysregulation.
Keywords	Science ; Q
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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