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Aging Cell Jun 2015Mammals differ more than 100-fold in maximum lifespan, which can be altered in either direction during evolution, but the molecular basis for natural changes in... (Review)
Review
Mammals differ more than 100-fold in maximum lifespan, which can be altered in either direction during evolution, but the molecular basis for natural changes in longevity is not understood. Divergent evolution of mammals also led to extensive changes in gene expression within and between lineages. To understand the relationship between lifespan and variation in gene expression, we carried out RNA-seq-based gene expression analyses of liver, kidney, and brain of 33 diverse species of mammals. Our analysis uncovered parallel evolution of gene expression and lifespan, as well as the associated life-history traits, and identified the processes and pathways involved. These findings provide direct insights into how nature reversibly adjusts lifespan and other traits during adaptive radiation of lineages.
Topics: Aging; Animals; Biological Evolution; Gene Expression; Humans; Longevity; Mammals; Molecular Sequence Data
PubMed: 25677554
DOI: 10.1111/acel.12283 -
Wiley Interdisciplinary Reviews. RNA May 2016Eukaryotic genomes produce thousands of diverse small RNAs (smRNAs), which play vital roles in regulating gene expression in all conditions, including in survival of... (Review)
Review
Eukaryotic genomes produce thousands of diverse small RNAs (smRNAs), which play vital roles in regulating gene expression in all conditions, including in survival of biotic and abiotic environmental stresses. SmRNA pathways intersect with most of the pathways regulating different steps in the life of a messenger RNA (mRNA), starting from transcription and ending at mRNA decay. SmRNAs function in both nuclear and cytoplasmic compartments; the regulation of mRNA stability and translation in the cytoplasm and the epigenetic regulation of gene expression in the nucleus are the main and best-known modes of smRNA action. However, recent evidence from animal systems indicates that smRNAs and RNA interference (RNAi) also participate in the regulation of alternative pre-mRNA splicing, one of the most crucial steps in the fast, efficient global reprogramming of gene expression required for survival under stress. Emerging evidence from bioinformatics studies indicates that a specific class of plant smRNAs, induced by various abiotic stresses, the sutr-siRNAs, has the potential to target regulatory regions within introns and thus may act in the regulation of splicing in response to stresses. This review summarizes the major types of plant smRNAs in the context of their mechanisms of action and also provides examples of their involvement in regulation of gene expression in response to environmental cues and developmental stresses. In addition, we describe current advances in our understanding of how smRNAs function in the regulation of pre-mRNA splicing. WIREs RNA 2016, 7:356-381. doi: 10.1002/wrna.1340 For further resources related to this article, please visit the WIREs website.
Topics: Gene Expression Regulation, Plant; Plant Physiological Phenomena; Protein Biosynthesis; RNA Splicing; RNA Stability; RNA, Small Untranslated; Stress, Physiological; Transcription, Genetic
PubMed: 26924473
DOI: 10.1002/wrna.1340 -
Advanced Science (Weinheim,... Mar 2023Major depressive disorder (MDD) is associated with structural and functional brain abnormalities. MDD as well as brain anatomy and function are influenced by genetic...
Major depressive disorder (MDD) is associated with structural and functional brain abnormalities. MDD as well as brain anatomy and function are influenced by genetic factors, but the role of gene expression remains unclear. Here, this work investigates how cortical gene expression contributes to structural and functional brain abnormalities in MDD. This work compares the gray matter volume and resting-state functional measures in a Chinese sample of 848 MDD patients and 749 healthy controls, and these case-control differences are then associated with cortical variation of gene expression. While whole gene expression is positively associated with structural abnormalities, it is negatively associated with functional abnormalities. This work observes the relationships of expression levels with brain abnormalities for individual genes, and found that transcriptional correlates of brain structure and function show opposite relations with gene dysregulation in postmortem cortical tissue from MDD patients. This work further identifies genes that are positively or negatively related to structural abnormalities as well as functional abnormalities. The MDD-related genes are enriched for brain tissue, cortical cells, and biological pathways. These findings suggest that distinct genetic mechanisms underlie structural and functional brain abnormalities in MDD, and highlight the importance of cortical gene expression for the development of cortical abnormalities.
Topics: Humans; Depressive Disorder, Major; Magnetic Resonance Imaging; Brain; Gray Matter; Brain Diseases; Gene Expression
PubMed: 36638259
DOI: 10.1002/advs.202205486 -
Mathematical Biosciences Dec 2023Multidisciplinary approaches can significantly advance our understanding of complex systems. For instance, gene co-expression networks align prior knowledge of...
Multidisciplinary approaches can significantly advance our understanding of complex systems. For instance, gene co-expression networks align prior knowledge of biological systems with studies in graph theory, emphasising pairwise gene to gene interactions. In this paper, we extend these ideas, promoting hypergraphs as an investigative tool for studying multi-way interactions in gene expression data. Additional freedoms are achieved by representing individual genes with hyperedges, and simultaneously testing each gene against many features/vertices. Further gene/hyperedge interactions can be captured and explored using the line graph representations, a technique that reduces the complexity of dense hypergraphs. Such an approach provides access to graph centrality measures, which identifies salient features within a data set. For instance dominant or hub-like hyperedges, leading to key knowledge on gene expression. The validity of this approach is established through the study of gene expression data for the plant species Senecio lautus and results will be interpreted within this biological setting.
Topics: Algorithms; Gene Regulatory Networks; Gene Expression
PubMed: 37914024
DOI: 10.1016/j.mbs.2023.109089 -
International Review of Neurobiology 2014The transcriptome changes hugely during development of the brain. Whole genes, alternate exons, and single base pair changes related to RNA editing all show differences... (Review)
Review
The transcriptome changes hugely during development of the brain. Whole genes, alternate exons, and single base pair changes related to RNA editing all show differences between embryonic and mature brain. Collectively, these changes control proteomic diversity as the brain develops. Additionally, there are many changes in noncoding RNAs (miRNA and lncRNA) that interact with mRNA to influence the overall transcriptional landscape. Here, we will discuss what is known about such changes in brain development, particularly focusing on high-throughput approaches and how those can be used to infer mechanisms by which gene expression is controlled in the brain as it matures.
Topics: Animals; Base Sequence; Brain; Gene Expression; Gene Expression Regulation, Developmental; Humans; RNA Splicing; Transcriptome
PubMed: 25172477
DOI: 10.1016/B978-0-12-801105-8.00009-6 -
Wiley Interdisciplinary Reviews. RNA 2010Maintenance of cellular function relies on the expression of genetic information with high fidelity, a process in which RNA molecules form an important link. mRNAs are... (Review)
Review
Maintenance of cellular function relies on the expression of genetic information with high fidelity, a process in which RNA molecules form an important link. mRNAs are intermediates that define the proteome, rRNAs and tRNAs are effector molecules that act together to decode mRNA sequence information, and small noncoding RNAs can regulate mRNA half-life and translatability. The steady-state levels of these RNAs occur through transcriptional and posttranscriptional regulatory mechanisms, of which RNA decay pathways are integral components. RNA decay can initiate from the ends of a transcript or through endonucleolytic cleavage, and numerous factors that catalyze or promote these reactions have been identified and characterized. The rate at which decay occurs depends on RNA sequence or structural elements and usually requires the RNA to be modified in a way that allows recruitment of the decay machinery to the transcript through the binding of accessory factors or small RNAs. The major RNA decay pathways also play important roles in the quality control (QC) of gene expression. Acting in both the nucleus and cytoplasm, multiple QC factors monitor newly synthesized transcripts, or mRNAs undergoing translation, for properties essential to function, including structural integrity or the presence of complete open-reading frames. Transcripts targeted by these surveillance mechanisms are rapidly shunted into conventional decay pathways where they are degraded rapidly to ensure that they do not interfere with the normal course of gene expression. Collectively, degradative mechanisms are important determinants of the extent of gene expression and play key roles in maintaining its accuracy.
Topics: Animals; Gene Expression; Humans; Models, Biological; Protein Binding; Protein Biosynthesis; Quality Control; RNA Stability; RNA, Messenger; RNA-Binding Proteins; Transcription, Genetic
PubMed: 21132108
DOI: 10.1002/wrna.25 -
Cells May 2022This overview presents recent evidence for a long-lasting PARP1 activation by a variety of signal transduction mechanisms, mediating signal-induced gene expression and... (Review)
Review
This overview presents recent evidence for a long-lasting PARP1 activation by a variety of signal transduction mechanisms, mediating signal-induced gene expression and chromatin remodeling. This mode of PARP1 activation has been reported in a variety of cell types, under physiological conditions. In this mechanism, PARP1 is not transiently activated by binding to DNA breaks. Moreover, damaged DNA interfered with this long-lasting PARP1 activation.
Topics: Chromatin Assembly and Disassembly; DNA Damage; Gene Expression
PubMed: 35563882
DOI: 10.3390/cells11091576 -
BMB Reports Feb 2019Cells must fine-tune their gene expression programs for optimal cellular activities in their natural growth conditions. Transcriptional memory, a unique transcriptional... (Review)
Review
Cells must fine-tune their gene expression programs for optimal cellular activities in their natural growth conditions. Transcriptional memory, a unique transcriptional response, plays a pivotal role in faster reactivation of genes upon environmental changes, and is facilitated if genes were previously in an active state. Hyper-activation of gene expression by transcriptional memory is critical for cellular differentiation, development, and adaptation. TREM (Transcriptional REpression Memory), a distinct type of transcriptional memory, promoting hyper-repression of unnecessary genes, upon environmental changes has been recently reported. These two transcriptional responses may optimize specific gene expression patterns, in rapidly changing environments. Emerging evidence suggests that they are also critical for immune responses. In addition to memory B and T cells, innate immune cells are transcriptionally hyperactivated by restimulation, with the same or different pathogens known as trained immunity. In this review, we briefly summarize recent progress in chromatin-based regulation of transcriptional memory, and its potential role in immune responses. [BMB Reports 2019; 52(2): 127-132].
Topics: Animals; Chromatin; Epigenesis, Genetic; Epigenomics; Galactokinase; Gene Expression; Gene Expression Regulation; Humans; Regulatory Elements, Transcriptional
PubMed: 30463643
DOI: 10.5483/BMBRep.2019.52.2.257 -
Biological Psychiatry Jan 2015Over the last decade, transcriptome studies of postmortem tissue from subjects with schizophrenia revealed that synaptic, mitochondrial, immune system,... (Review)
Review
Over the last decade, transcriptome studies of postmortem tissue from subjects with schizophrenia revealed that synaptic, mitochondrial, immune system, gamma-aminobutyric acidergic, and oligodendrocytic changes are all integral parts of the disease process. The combined genetic and transcriptomic studies argue that the molecular underpinnings of the disease are even more varied than the symptomatic diversity of schizophrenia. Ultimately, to decipher the pathophysiology of human disorders in general, we will need to understand the function of hundreds of genes and regulatory elements in our genome and the consequences of their overexpression and reduced expression in a developmental context. Furthermore, integration of knowledge from various data sources remains a monumental challenge that has to be systematically addressed in the upcoming decades. In the end, our success in interpreting the molecular changes in schizophrenia will depend on our ability to understand the biology using innovative ideas and cannot depend on the hope of developing novel, more powerful technologies.
Topics: Animals; Gene Expression; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Schizophrenia; Signal Transduction; Transcriptome
PubMed: 24507510
DOI: 10.1016/j.biopsych.2014.01.001 -
Seminars in Cell & Developmental Biology Apr 2018Our most distinguishing higher cognitive functions are controlled by the cerebral cortex. Comparative studies detail abundant anatomical and cellular features unique to... (Review)
Review
Our most distinguishing higher cognitive functions are controlled by the cerebral cortex. Comparative studies detail abundant anatomical and cellular features unique to the human developing and adult neocortex. Emerging genomic studies have further defined vast differences distinguishing developing human neocortices from related primates. These human-specific changes can affect gene function and/or expression, and result from structural variations such as chromosomal deletions and duplications, or from point mutations in coding and noncoding regulatory regions. Here, we review this rapidly growing field which aims to identify and characterize genetic loci unique to the human cerebral cortex. We catalog known human-specific genomic changes distinct from other primates, including those whose function has been interrogated in animal models. We also discuss how new model systems and technologies such as single cell RNA sequencing, primate iPSCs, and gene editing, are enabling the field to gain unprecedented resolution into function of these human-specific changes. Some neurological disorders are thought to uniquely present in humans, thus reinforcing the need to comprehensively understand human-specific gene expression in the developing brain.
Topics: Biological Evolution; Gene Expression; Genomics; Humans
PubMed: 28864345
DOI: 10.1016/j.semcdb.2017.08.045