scholarly journals The functions of natural antisense transcripts

2013 ◽  
Vol 54 ◽  
pp. 91-101 ◽  
Author(s):  
Megan Wight ◽  
Andreas Werner
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Mechanisms Of Action ◽  
Transcriptional Interference ◽  
Antisense Transcripts ◽  
Specific Expression ◽  
Natural Antisense Transcripts ◽  
Regulatory Impact ◽  
Regulatory Rnas ◽  
Eukaryotic Genomes

NATs (natural antisense transcripts) are widespread in eukaryotic genomes. Experimental evidence indicates that sense and antisense transcripts interact, suggesting a role for NATs in the regulation of gene expression. On the other hand, the transcription of a gene locus in both orientations and RNA hybrid formation can also lead to transcriptional interference, trigger an immune response or induce gene silencing. Tissue-specific expression of NATs and the compartmentalization of cells ensure that the regulatory impact of NATs prevails. Consequently, NATs are now acknowledged as important modulators of gene expression. New mechanisms of action and important biological roles of NATs keep emerging, making regulatory RNAs an exciting and quickly moving area of research.

scholarly journals Cell-type Specific Expression Quantitative Trait Loci Associated with Alzheimer Disease in Blood and Brain Tissue

2020 ◽  
Author(s):  
Devanshi Patel ◽  
Xiaoling Zhang ◽  
John J. Farrell ◽  
Jaeyoon Chung ◽  
Thor D. Stein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Eqtl Analysis ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

ABSTRACTBecause regulation of gene expression is heritable and context-dependent, we investigated AD-related gene expression patterns in cell-types in blood and brain. Cis-expression quantitative trait locus (eQTL) mapping was performed genome-wide in blood from 5,257 Framingham Heart Study (FHS) participants and in brain donated by 475 Religious Orders Study/Memory & Aging Project (ROSMAP) participants. The association of gene expression with genotypes for all cis SNPs within 1Mb of genes was evaluated using linear regression models for unrelated subjects and linear mixed models for related subjects. Cell type-specific eQTL (ct-eQTL) models included an interaction term for expression of “proxy” genes that discriminate particular cell type. Ct-eQTL analysis identified 11,649 and 2,533 additional significant gene-SNP eQTL pairs in brain and blood, respectively, that were not detected in generic eQTL analysis. Of note, 386 unique target eGenes of significant eQTLs shared between blood and brain were enriched in apoptosis and Wnt signaling pathways. Five of these shared genes are established AD loci. The potential importance and relevance to AD of significant results in myeloid cell-types is supported by the observation that a large portion of GWS ct-eQTLs map within 1Mb of established AD loci and 58% (23/40) of the most significant eGenes in these eQTLs have previously been implicated in AD. This study identified cell-type specific expression patterns for established and potentially novel AD genes, found additional evidence for the role of myeloid cells in AD risk, and discovered potential novel blood and brain AD biomarkers that highlight the importance of cell-type specific analysis.

scholarly journals What are natural antisense transcripts good for?

2010 ◽  
Vol 38 (4) ◽  
pp. 1144-1149 ◽  
Author(s):  
Andreas Werner ◽  
Daniel Swan
Keyword(s):  
Gene Expression ◽  
Gene Silencing ◽  
Higher Order ◽  
Transcriptional Gene Silencing ◽  
Antisense Transcripts ◽  
Natural Antisense Transcripts ◽  
Protein Coding ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene

NATs (natural antisense transcripts) are important regulators of eukaryotic gene expression. Interference between the expression of protein-coding sense transcripts and the corresponding NAT is well documented. In the present review, we focus on an additional, higher-order role of NATs that is currently emerging. The recent discovery of endogenous siRNAs (short interfering RNAs), as well as NAT-induced transcriptional gene silencing, are key to the proposed novel function of NATs.

scholarly journals Roles of Transposable Elements in the Different Layers of Gene Expression Regulation

2019 ◽  
Vol 20 (22) ◽  
pp. 5755 ◽  
Author(s):  
Denise Drongitis ◽  
Francesco Aniello ◽  
Laura Fucci ◽  
Aldo Donizetti
Keyword(s):  
Gene Expression ◽  
Transposable Elements ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Chromatin Modification ◽  
Essential Element ◽  
Protein Translation ◽  
Expression Regulation ◽  
Molecular Processes ◽  
Eukaryotic Genomes

The biology of transposable elements (TEs) is a fascinating and complex field of investigation. TEs represent a substantial fraction of many eukaryotic genomes and can influence many aspects of DNA function that range from the evolution of genetic information to duplication, stability, and gene expression. Their ability to move inside the genome has been largely recognized as a double-edged sword, as both useful and deleterious effects can result. A fundamental role has been played by the evolution of the molecular processes needed to properly control the expression of TEs. Today, we are far removed from the original reductive vision of TEs as “junk DNA”, and are more convinced that TEs represent an essential element in the regulation of gene expression. In this review, we summarize some of the more recent findings, mainly in the animal kingdom, concerning the active roles that TEs play at every level of gene expression regulation, including chromatin modification, splicing, and protein translation.

scholarly journals Enhancing enhancers: new complexities in the retinoid regulation of gene expression

2004 ◽  
Vol 383 (1) ◽  
Author(s):  
Chris P. F. REDFERN
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Regulation Of Gene Expression ◽  
Specific Expression ◽  
Response Element ◽  
Hormone Response Elements ◽  
Signalling Molecules ◽  
Biochemical Journal ◽  
Signalling Molecule ◽  
X Receptors

Retinoic acid is a signalling molecule central to morphogenesis and musculoskeletal development. It can exist in several isomeric forms, of which all-trans- and 9-cis-retinoic acid are thought to be the most relevant as signalling molecules. Retinoic acid regulates gene expression via RARs (retinoic acid receptors) working as heterodimers with RXRs (retinoid X receptors). RXRs also heterodimerize with other nuclear receptors. In this issue of the Biochemical Journal, Harris et al. have shown that an enhancer responsible for chondrocyte-specific expression of the col11a2 gene is itself regulated by a retinoic-acid-dependent interaction with RXRβ bound to a downstream response element. Thus, RXRs bound to hormone-response elements can regulate gene expression indirectly via interactions with tissue-specific enhancers. This study raises interesting questions about the nature of the response element, the RXRβ partner and the ligands able to influence col11a2 expression, and will provide a model system with which to understand tissue and ligand specificity of retinoid responses.

scholarly journals The genetic basis of evolutionary change in gene expression levels

2010 ◽  
Vol 365 (1552) ◽  
pp. 2581-2590 ◽  
Author(s):  
J. J. Emerson ◽  
Wen-Hsiung Li
Keyword(s):  
Gene Expression ◽  
Genetic Basis ◽  
Regulation Of Gene Expression ◽  
Specific Expression ◽  
Genetic Changes ◽  
Expression Variation ◽  
Regulatory Variation ◽  
Global Mapping ◽  
History Of ◽  
Trait Locus

The regulation of gene expression is an important determinant of organismal phenotype and evolution. However, the widespread recognition of this fact occurred long after the synthesis of evolution and genetics. Here, we give a brief sketch of thoughts regarding gene regulation in the history of evolution and genetics. We then review the development of genome-wide studies of gene regulatory variation in the context of the location and mode of action of the causative genetic changes. In particular, we review mapping of the genetic basis of expression variation through expression quantitative trait locus studies and measuring the cis / trans component of expression variation in allele-specific expression studies. We conclude by proposing a systematic integration of ideas that combines global mapping studies, cis / trans tests and modern population genetics methodologies, in order to directly estimate the forces acting on regulatory variation within and between species.

scholarly journals A Novel Biological Role of Tachykinins as an Up-Regulator of Oocyte Growth: Identification of an Evolutionary Origin of Tachykininergic Functions in the Ovary of the Ascidian, Ciona intestinalis

Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4346-4356 ◽  
Author(s):  
Masato Aoyama ◽  
Tsuyoshi Kawada ◽  
Manabu Fujie ◽  
Kohji Hotta ◽  
Tsubasa Sakai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Model Organism ◽  
Ciona Intestinalis ◽  
Enzymatic Activities ◽  
Evolutionary Origin ◽  
Phylogenetic Position ◽  
Specific Expression ◽  
Oocyte Growth ◽  
Vitellogenic Stage

Tachykinins (TKs) and their receptors have been shown to be expressed in the mammalian ovary. However, the biological roles of ovarian TKs have yet to be verified. Ci-TK-I and Ci-TK-R, characterized from the protochordate (ascidian), Ciona intestinalis, are prototypes of vertebrate TKs and their receptors. In the present study, we show a novel biological function of TKs as an inducible factor for oocyte growth using C. intestinalis as a model organism. Immunostaining demonstrated the specific expression of Ci-TK-R in test cells residing in oocytes at the vitellogenic stage. DNA microarray and real-time PCR revealed that Ci-TK-I induced gene expression of several proteases, including cathepsin D, chymotrypsin, and carboxy-peptidase B1, in the ovary. The enzymatic activities of these proteases in the ovary were also shown to be enhanced by Ci-TK-I. Of particular significance is that the treatment of Ciona oocytes with Ci-TK-I resulted in progression of growth from the vitellogenic stage to the post-vitellogenic stage. The Ci-TK-I-induced oocyte growth was blocked by a TK antagonist or by protease inhibitors. These results led to the conclusion that Ci-TK-I enhances growth of the vitellogenic oocytes via up-regulation of gene expression and enzymatic activities of the proteases. This is the first clarification of the biological roles of TKs in the ovary and the underlying essential molecular mechanism. Furthermore, considering the phylogenetic position of ascidians as basal chordates, we suggest that the novel TK-regulated oocyte growth is an “evolutionary origin” of the tachykininergic functions in the ovary.

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