Bioinformatics Analyses of the Transcriptome Reveal Ube3a-Dependent Effects on Mitochondrial-Related Pathways.

International Journal of Molecular Sciences
Julia PanovHanoch Kaphzan

Abstract

The UBE3A gene encodes the ubiquitin E3-ligase protein, UBE3A, which is implicated in severe neurodevelopmental disorders. Lack of UBE3A expression results in Angelman syndrome, while UBE3A overexpression, due to genomic 15q duplication, results in autism. The cellular roles of UBE3A are not fully understood, yet a growing body of evidence indicates that these disorders involve mitochondrial dysfunction and increased oxidative stress. We utilized bioinformatics approaches to delineate the effects of murine Ube3a deletion on the expression of mitochondrial-related genes and pathways. For this, we generated an mRNA sequencing dataset from mouse embryonic fibroblasts (MEFs) in which both alleles of Ube3a gene were deleted and their wild-type controls. Since oxidative stress and mitochondrial dysregulation might not be exhibited in the resting baseline state, we also activated mitochondrial functioning in the cells of these two genotypes using TNFα application. Transcriptomes of the four groups of MEFs, Ube3a+/+ and Ube3a-/-, with or without the application of TNFα, were analyzed using various bioinformatics tools and machine learning approaches. Our results indicate that Ube3a deletion affects the gene expression profiles of mitoc...Continue Reading

References

Jul 1, 1990·Journal of Child Neurology·O Eeg-OlofssonM M Al-Essa
Jan 1, 1997·Nature Genetics·T KishinoJ Wagstaff
Jul 1, 1997·The American Journal of Physiology·J C Fernández-ChecaA Morales
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·Z NawazB W O'Malley
Dec 11, 1999·Nucleic Acids Research·M Kanehisa, S Goto
Mar 21, 2001·Apoptosis : an International Journal on Programmed Cell Death·H U SimonF Levi-Schaffer
Jun 5, 2003·Annals of Neurology·Pauline A FilipekJ Jay Gargus
Jun 20, 2006·Molecular and Cellular Biology·Skirmantas KriaucionisAdrian Bird
Oct 20, 2006·The Journal of Biological Chemistry·Jun LiuVassilios Papadopoulos
Jan 26, 2008·Cell Death and Differentiation·T Klimova, N S Chandel
Apr 25, 2008·Nuclear Receptor Signaling·Sivapriya Ramamoorthy, Zafar Nawaz
Jun 19, 2008·Molecular and Cellular Biology·Amina A Qutub, Aleksander S Popel
Jul 5, 2008·Cancer Cell·Francesca BernassolaGerry Melino
Jun 30, 2009·Antioxidants & Redox Signaling·Montserrat MaríJosé C Fernández-Checa
Aug 8, 2009·Annual Review of Genetics·Chunxin Wang, Richard J Youle
Mar 3, 2010·Journal of Inherited Metabolic Disease·Sander Michel Houten, Ronald J A Wanders
Jul 24, 2010·Annals of the New York Academy of Sciences·Robin A J Smith, Michael P Murphy
Sep 4, 2010·Pharmacology & Therapeutics·Ian A ClarkBryce Vissel
Sep 11, 2010·Molecular Endocrinology·Sivapriya RamamoorthyZafar Nawaz
Dec 1, 2008·Journal of the American Statistical Association·Carlos M CarvalhoMike West
Oct 5, 2011·Antioxidants & Redox Signaling·Valeria Gabriela Antico ArciuchMaría Cecilia Carreras
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
May 31, 2012·Molecular and Cellular Biology·Gustavo Martínez-NoëlPeter M Howley
Jan 4, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sheng MiaoZhi-Qi Xiong
Mar 2, 2013·Human Molecular Genetics·Hideaki MatsuiRyosuke Takahashi
Mar 16, 2013·Autism Research : Official Journal of the International Society for Autism Research·Nora UrracaLawrence T Reiter
Sep 5, 2013·Cold Spring Harbor Perspectives in Biology·Stephen W G Tait, Douglas R Green
Nov 5, 2013·Journal of Molecular Signaling·Shidrokh ArdestaniPampee P Young
Apr 4, 2014·Bioinformatics·Anthony M BolgerBjoern Usadel
Jul 16, 2014·Frontiers in Pharmacology·Vicent RibasJosé C Fernández-Checa

❮ Previous
Next ❯

Citations

Feb 4, 2021·Biomedicines·Paola Bressan, Peter Kramer
Feb 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Tal YardeniDouglas C Wallace

❮ Previous
Next ❯

Datasets Mentioned

BETA
PRJNA48422
SRP044749

Methods Mentioned

BETA
electron microscopy
PCA
Illumina sequencing
PCR
RNA-seq

Software Mentioned

DAVID
Heatmapper
R MASS package
Trimmomatic
HTSeq
DeSeq2
RSEM
random Forest R

Related Concepts

Related Feeds

Autism

Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.

Angelman Syndrome

Angelman syndrome is a neurogenetic imprinting disorder caused by loss of the maternally inherited UBE3A gene and is characterized by generalized epilepsy, limited expressive speech, sleep dysfunction, and movement disorders. Here is the latest research.