scholarly journals PiggyBac Transposable Element-derived 1 controls Neuronal Progenitor Identity, Stress Sensing and mammal-specific paraspeckles

2021 ◽  
Author(s):  
Tamas Rasko ◽  
Amit Pande ◽  
Kathrin Radscheit ◽  
Annika Zink ◽  
Manvendra Singh ◽  
...  

The evolution and functional integration of new genes, especially those that become core to key functions, remains enigmatic. We consider the mammal-specific gene, piggyBac transposable element derived 1 (PGBD1), implicated in neuronal disorders. While it no longer recognises piggyBac transposon-like inverted repeats and transposase functionality having been lost, it has evolved a core role in neural homeostasis. Depletion of PGBD1 triggers accumulation of mammal-specific paraspeckles and neural differentiation. It acts by two modalities, DNA binding and protein-protein interaction. As a transcriptional repressor of (lnc)NEAT1, the backbone of paraspeckles, it inhibits paraspeckle formation in neural progenitor cells (NPCs). At the protein level it is associated with the stress response system, a function partially shared with (lnc)NEAT1. PGBD1 thus presents as an unusual exemplar of new gene creation, being a recently acquired multi-function, multi-modal gene. Mammalian specificity associated with control of a mammal-specific structure implies coevolution of new genes with new functions.

2021 ◽  
Author(s):  
Yuan Huang ◽  
Jiahui Chen ◽  
Chuan Dong ◽  
Dylan Sosa ◽  
Shengqian Xia ◽  
...  

Abstract Gene duplication is increasingly recognized as an important mechanism for the origination of new genes, as revealed by comparative genomic analysis. However, how new duplicate genes contribute to phenotypic evolution remains largely unknown, especially in plants. Here, we identified the new gene EXOV, derived from a partial gene duplication of its parental gene EXOVL in Arabidopsis thaliana. EXOV is a species-specific gene that originated within the last 3.5 million years and shows strong signals of positive selection. Unexpectedly, RNA-seq analyses revealed that, despite its young age, EXOV has acquired many novel direct and indirect interactions in which the parental gene does not engage. This observation is consistent with the high, selection-driven substitution rate of its encoded protein, in contrast to the slowly evolving EXOVL, suggesting an important role for EXOV in phenotypic evolution. We observed significant differentiation of morphological changes for all phenotypes assessed in genome-edited and T-DNA insertional single mutants and in double T-DNA insertion mutants in EXOV and EXOVL. We discovered a substantial divergence of phenotypic effects by principal component analyses, suggesting neofunctionalization of the new gene. These results reveal a young gene that plays critical roles in biological processes that underlie morphological evolution in A. thaliana.


2017 ◽  
Vol 3 (2) ◽  
pp. 38 ◽  
Author(s):  
Vladislava Milchevskaya ◽  
Grischa Tödt ◽  
Toby James Gibson

Genome-wide expression profiling and genotyping is widely applied in functional genomics research, ranging from stem cell studies to cancer, in drug response studies, and in clinical diagnostics. The Affymetrix GeneChip microarrays represent the most popular platform for such assays. Nevertheless, due to rapid and continuous improvement of the knowledge about the genome, the definition of many of the genes and transcripts change, and new genes are discovered. Thus the original probe information is out-dated for a number of Affymetrix platforms, and needs to be re-defined. It has been demonstrated, that accurate probe set definition improves both coverage of the gene expression analysis and its statistical power. Therefore we developed a method that incorporates the most recent genome annotations into the annotation of the microarray probe sets, using tools from the next generation sequencing. Additionally our method allows to quickly build project specific gene annotation models, as well as for comparison of microarray to RNAseq data.


2019 ◽  
Author(s):  
T. Reid Alderson ◽  
Elias Adriaenssens ◽  
Bob Asselbergh ◽  
Iva Pritišanac ◽  
Heidi Y. Gastall ◽  
...  

HSP27 (HSPB1) is a systemically expressed human small heat-shock protein that forms large, dynamic oligomers and functions in various aspects of cellular homeostasis. Mutations in HSP27 cause Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. A particularly severe form of the disease is triggered by the P182L mutation within the highly conserved IxI/V motif of HSP27. Here, we observed that the P182L variant of HSP27 lacks the ability to prevent the aggregation of client proteins and formed significantly larger oligomers both in vitro and in vivo. NMR spectroscopy revealed that the P182L IxI/V motif binds its α-crystallin domain with significantly lower association rate, and thus affinity, rendering the binding site more available for other interactors. We identified 22 IxI/V-containing proteins that are known to interact with HSP27 and could therefore bind with enhanced affinity to the P182L variant. We validated this hypothesis through co-immunoprecipitation experiments, revealing that the IxI/V motif-bearing co-chaperone BAG3 indeed binds with higher affinity to the P182L variant. Our results provide a mechanistic basis for the impact of the P182L mutation on HSP27, and highlight the general importance of the IxI/V motif and its role in protein-protein interaction networks.


2017 ◽  
Vol 12 (3) ◽  
pp. 462-483 ◽  
Author(s):  
Rebeca Geffin ◽  
Ricardo Martinez ◽  
Alicia de las Pozas ◽  
Biju Issac ◽  
Micheline McCarthy

2019 ◽  
Vol 20 (7) ◽  
pp. 1796 ◽  
Author(s):  
Lorenzo Corsi ◽  
Andrea Mescola ◽  
Andrea Alessandrini

Glioblastoma multiforme (GBM) is the most aggressive malignant tumor of the central nervous system, with poor survival in both treated and untreated patients. Recent studies began to explain the molecular pathway, comprising the dynamic structural and mechanical changes involved in GBM. In this context, some studies showed that the human glioblastoma cells release high levels of glutamate, which regulates the proliferation and survival of neuronal progenitor cells. Considering that cancer cells possess properties in common with neural progenitor cells, it is likely that the functions of glutamate receptors may affect the growth of cancer cells and, therefore, open the road to new and more targeted therapies.


2000 ◽  
Vol 279 (3) ◽  
pp. F426-F439 ◽  
Author(s):  
Erding Hu ◽  
Zunxuan Chen ◽  
Todd Fredrickson ◽  
Miklos Gellai ◽  
Malcolm Jugus ◽  
...  

To gain further insights into the molecular mechanisms involved in acute renal failure, we have isolated a new gene from rat and human, named KSP32 (kidney-specific protein with a molecular mass of 32 kDa). KSP32 encodes a novel gene that shows little homology to other mammalian proteins. It, however, shares extensive homology with several proteins found in the nematode Caenorhabditis elegans and plants. The expression of KSP32 mRNA is highly restricted to kidney. In situ hybidization analysis revealed that the expression of KSP32 mRNA was prominent in the boundary of kidney cortex and outer medulla, exhibiting a raylike formation extending from the medulla into the cortex. Finally, KSP32 mRNA was dramatically downregulated in rat following induction of acute ischemic renal failure. Rapid loss of KSP32 mRNA expression was observed beginning at ∼5 h following renal injury and mRNA levels remained depressed for at least 96 h. Both KSP32 mRNA levels as well as renal function recovered 14 days after injury. Administration of an endothelin receptor antagonist (SB-209670), known to restore renal function, significantly increased KSP32 expression.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Raphaëlle Dubruille ◽  
Gabriel A. B. Marais ◽  
Benjamin Loppin

Comparative genome analysis has allowed the identification of various mechanisms involved in gene birth. However, understanding the evolutionary forces driving new gene origination still represents a major challenge. In particular, an intriguing and not yet fully understood trend has emerged from the study of new genes: many of them show a testis-specific expression pattern, which has remained poorly understood. Here we review the case of such a new gene, which involves a telomere-capping gene family in Drosophila. hiphop and its testis-specific paralog K81 are critical for the protection of chromosome ends in somatic cells and male gametes, respectively. Two independent functional studies recently proposed that these genes evolved under a reproductive-subfunctionalization regime. The 2011 release of new Drosophila genome sequences from the melanogaster group of species allowed us to deepen our phylogenetic analysis of the hiphop/K81 family. This work reveals an unsuspected dynamic of gene birth and death within the group, with recurrent duplication events through retroposition mechanisms. Finally, we discuss the plausibility of different evolutionary scenarios that could explain the diversification of this gene family.


2017 ◽  
Vol 17 (5) ◽  
pp. 1213-1224 ◽  
Author(s):  
Namgyu Kim ◽  
Hae-Bum Yun

A novel noncontact, mobile sensing technique to measure absolute stress in rail using photoluminescence piezospectroscopy is presented. Photoluminescence piezospectroscopy is a vibrational spectroscopy technique for chemical identification and stress measurement by focusing low-power laser on a substance surface. Thermite welding is a major welding method for continuous welded rail, which produces iron (Fe) and aluminum oxides (Al2O3) after aluminothermic reaction. Photoluminescence piezospectroscopy was used as a noncontact stress sensing method since photoluminescence piezospectroscopy has an excellent detectability for alpha-phase aluminum oxide (α-Al2O3). Using a portable photoluminescence piezospectroscopy system, a prominent α-Al2O3 signal was collected from the bare surface of thermite weld samples. A loading frame test was conducted to determine the piezospectroscopic coefficient of α-Al2O3 in thermite weld. A pulverization method is introduced to determine absolute stress from an existing rail sample. The experimental results show many advantages of this method over traditional methods to measure stress in rail as a mobile sensing method.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4767-4767
Author(s):  
Hai Fang ◽  
Kankan Wang ◽  
Ji Zhang

Abstract Hematopoietic stem cells and their progenitor hierarchy are highly controlled by the underlying gene regulatory network. In past decades, great progress has been made in elucidating lineage-restricted transcription factors and lineage-specific gene expression patterns. With accumulation of genome-wide biological data, it is of great value to expand beyond mere transcriptional regulatory analysis to the systemic understanding. Here, we utilized a probabilistic integrated gene network for integrating heterogeneous functional genomic and proteomic data sources into predictive model of hematopoietic lineage diversification. We first constructed a naïve Bayesian network by incorporating disparate biological data, including time-series gene expression during re-dedifferentiation of leukemia along alternative paths into granulocyte or monocyte upon the treatment of differentiation-inducing agents, computationally generated transcription factor regulatory sites and microRNA targets, well-curated physical protein-protein interaction, and functional annotation data. The resultant network, coupled with binomial-based statistical analysis of the interplay between node properties and the network topology, predicted the specific hematopoietic lineage, generating testable hypotheses regarding their unified reprogramming principles. This study demonstrates the utility of the growing biological data in detailed elucidations of the orchestration of distinct hematopoietic cell fates.


1961 ◽  
Vol 39 (3) ◽  
pp. 513-518 ◽  
Author(s):  
J. N. Welsh ◽  
G. J. Green ◽  
R. I. H. McKenzie

The inheritance in oats of reaction to some new races and to some well-known races of oat stem rust, Puccinia graminis Pers. f. sp. avenae Erikss. and Henn., was investigated in the crosses Jostrain × Eagle, Canuck × Cherokee, and R.L. 524.1 (Hajira × Banner) × Eagle. The resistance of the variety Jostrain to races 1, 3, 4, 13, and 13A was conferred by a single gene, here designated as the E gene in accordance with the practice of designating genes for stem rust resistance by capital letters. Canuck, a derivative of Jostrain, carries the new E gene and the previously identified B gene. The resistance of R.L. 524.1 to all races is conferred by two major genes and a modifying gene. One of the major genes acts like the well-known B gene which confers resistance to all races except 6A, 7A, 8A, and 13A. The other major gene apparently is a new gene in oats for resistance to stem rust and is here designated the F gene. The F gene confers resistance to all races but a modifying gene is required along with it for resistance to race 7.


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