Genetic compensation: A phenomenon in search of mechanisms.
TLDR
This review revisits studies reporting genetic compensation in higher eukaryotes and outlines possible molecular mechanisms, which may include both transcriptional and posttranscriptional processes.Abstract:
Several recent studies in a number of model systems including zebrafish, Arabidopsis, and mouse have revealed phenotypic differences between knockouts (i.e., mutants) and knockdowns (e.g., antisense-treated animals). These differences have been attributed to a number of reasons including off-target effects of the antisense reagents. An alternative explanation was recently proposed based on a zebrafish study reporting that genetic compensation was observed in egfl7 mutant but not knockdown animals. Dosage compensation was first reported in Drosophila in 1932, and genetic compensation in response to a gene knockout was first reported in yeast in 1969. Since then, genetic compensation has been documented many times in a number of model organisms; however, our understanding of the underlying molecular mechanisms remains limited. In this review, we revisit studies reporting genetic compensation in higher eukaryotes and outline possible molecular mechanisms, which may include both transcriptional and posttranscriptional processes.read more
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Journal Article
Genetic compensation induced by deleterious mutations but not gene knockdowns
TL;DR: In this article, the authors show that egfl7 mutants do not show any obvious phenotypes while animals injected with egfl 7 morpholino (morphants) exhibit severe vascular defects, indicating that the activation of a compensatory network to buffer against deleterious mutations was not observed after translational or transcriptional knockdown.
Journal ArticleDOI
Genetic compensation triggered by mutant mRNA degradation
Mohamed A. El-Brolosy,Zacharias Kontarakis,Andrea Rossi,Andrea Rossi,Carsten Kuenne,Stefan Günther,Nana Fukuda,Khrievono Kikhi,Giulia L. M. Boezio,Carter M. Takacs,Carter M. Takacs,Shih-Lei Lai,Shih-Lei Lai,Ryuichi Fukuda,Claudia Gerri,Claudia Gerri,Antonio J. Giraldez,Didier Y.R. Stainier +17 more
TL;DR: Transcriptional adaptation, a genetic compensation process by which organisms respond to mutations by upregulating related genes, is triggered by mRNA decay and involves a sequence-dependent mechanism.
Transcriptome-wide Mapping Reveals Widespread Dynamic-Regulated Pseudouridylation of ncRNA and mRNA
Schraga Schwartz,Douglas A. Bernstein,Maxwell R. Mumbach,Marko Jovanovic,Rebecca H. Herbst,Brian X. León-Ricardo,Jesse M. Engreitz,Mitchell Guttman,Rahul Satija,Eric S. Lander,Gerald R. Fink,Aviv Regev,Aviv Regev,Aviv Regev +13 more
TL;DR: This work identifies an enhanced, transcriptome-wide scope for pseudouridine and methods to dissect its underlying mechanisms and function and discovers hundreds of unique sites in human and yeast mRNAs and snoRNAs.
Journal ArticleDOI
IGF-Binding Proteins: Why Do They Exist and Why Are There So Many?
John B. Allard,Cunming Duan +1 more
TL;DR: The emerging explanation that many IGFBP functions have evolved to allow the targeted adjustment of IGF signaling under stressful or irregular conditions, which would likely not be revealed in a standard laboratory setting are explored.
Journal ArticleDOI
Highly Efficient CRISPR-Cas9-Based Methods for Generating Deletion Mutations and F0 Embryos that Lack Gene Function in Zebrafish
Kazuyuki Hoshijima,Michael J. Jurynec,Dana Klatt Shaw,Ashley M. Jacobi,Mark A. Behlke,David Grunwald +5 more
TL;DR: Supernumerary guanine nucleotides at the 5' ends of single guide RNAs (sgRNAs) account for diminished CRISPR-Cas9 activity in zebrafish embryos and heritable deletion mutations of at least 50 kbp can be readily induced using pairs of duplex guide RNPs targeted to a single chromosome.
References
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TL;DR: It appears that many mutations are conditional and/or do not alter plant morphology even in the presence of severe physiological defects, and gene knockout per se is not sufficient to assess gene function and must be integrated into a more global approach for determining biological functions.
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