TULA‐family proteins: Jacks of many trades and then some

Tsygankov, Alexander Y.

doi:10.1002/jcp.26890

Cited by 15 publications

(18 citation statements)

References 95 publications

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“…The mammalian ortholog of CG4025 (DRAM1/2) is induced by p53 in response to DNA damage and promotes apoptosis and autophagy (Guan et al, 2015). The mammalian orthologs of CG13604 (UBASH3A/B) are tyrosine phosphatases that repress SYK kinase, an enzyme reported to help protect cells against ROS, with superoxide activation of Drosophila Syk kinase signalling tissue injury (Secchi et al, 2015; Srinivasan et al, 2016; Tsygankov, 2018). Finally, the ortholog of CG3709 in archaea has tRNA pseudouridine synthase activity, but the human ortholog PUS10 has been reported to be cleaved during apoptosis and promote caspase-3 activity, thus its loss may slow apopotic cell death (Jana et al, 2017).…”

Section: Resultsmentioning

confidence: 99%

Functional unknomics: closing the knowledge gap to accelerate biomedical research

Rocha

Jayaram

Stevens

et al. 2022

Preprint

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The human genome encodes ~20,000 proteins, many still uncharacterised. Scientific and social factors have resulted in a focus on well-studied proteins, leading to a concern that poorly understood genes are unjustifiably neglected. To address this, we have developed an "Unknome database" that ranks proteins based on how little is known about them. We applied RNAi in Drosophila to 260 unknown genes that are conserved between flies and humans. About a quarter are required for viability, and functional screening of the rest revealed hits for fertility, development, locomotion, protein quality control and resilience to stress. CRISPR/Cas9 gene disruption validated a component of Notch signalling and two genes contributing to male fertility. Our work demonstrates the importance of poorly understood genes, provides a resource for future research acceleration, and highlights a need for our awareness of ignorance to be protected from erosion by automated database annotation.

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Section: Resultsmentioning

confidence: 99%

Functional unknomics: closing the knowledge gap to accelerate biomedical research

Rocha

Jayaram

Stevens

et al. 2022

Preprint

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“…Gene-level FPKM (fragments per kilobase of gene per million read pairs) were extracted from the gene abundance output files produced by StringTie and merged into a gene expression matrix (GEM) using a PBS-GEM Perl script. The matrix was log 2 transformed and preprocessed using the preprocessCore R library (Tsygankov, 2018) to detect outliers and reduce technical noise. Pairwise Kolmogorov-Smirnov (KS) tests were performed to test for outlier samples (KS Dval > 0.15).…”

Section: Methodsmentioning

confidence: 99%

Identifying Temporally Regulated Root Nodulation Biomarkers Using Time Series Gene Co-Expression Network Analysis

et al. 2019

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Root nodulation results from a symbiotic relationship between a plant host and Rhizobium bacteria. Synchronized gene expression patterns over the course of rhizobial infection result in activation of pathways that are unique but overlapping with the highly conserved pathways that enable mycorrhizal symbiosis. We performed RNA sequencing of 30 Medicago truncatula root maturation zone samples at five distinct time points. These samples included plants inoculated with Sinorhizobium medicae and control plants that did not receive any Rhizobium. Following gene expression quantification, we identified 1,758 differentially expressed genes at various time points. We constructed a gene co-expression network (GCN) from the same data and identified link community modules (LCMs) that were comprised entirely of differentially expressed genes at specific time points post-inoculation. One LCM included genes that were up-regulated at 24 h following inoculation, suggesting an activation of allergen family genes and carbohydrate-binding gene products in response to Rhizobium. We also identified two LCMs that were comprised entirely of genes that were down regulated at 24 and 48 h post-inoculation. The identity of the genes in these modules suggest that down-regulating specific genes at 24 h may result in decreased jasmonic acid production with an increase in cytokinin production. At 48 h, coordinated down-regulation of a specific set of genes involved in lipid biosynthesis may play a role in nodulation. We show that GCN-LCM analysis is an effective method to preliminarily identify polygenic candidate biomarkers of root nodulation and develop hypotheses for future discovery.

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“…Ubiquitin associated and SH3 domain containing A (UBASH3A) gene is mapped to chromosome 21q22.3 [35]. Its expression is thought to be restricted to lymphoid tissues and primarily T cells [36].…”

Section: Introductionmentioning

confidence: 99%

“…Its expression is thought to be restricted to lymphoid tissues and primarily T cells [36]. Genetic studies on mouse models revealed that simultaneous deletion of Ubash3a and Ubash3b causes hyperreactivity of T cells due to their involvement in the regulation of protein tyrosine kinase-mediated signaling [35]. UBASH3A participates in pro-apoptotic pathways by binding to AIF independently of caspase apoptotic events [37].…”

Section: Introductionmentioning

confidence: 99%

CRKL, AIFM3, AIF, BCL2, and UBASH3A during Human Kidney Development

Lozić

Minarik

Racetin

et al. 2021

IJMS

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We aimed to investigate the spatio-temporal expression of possible CAKUT candidate genes CRKL, AIFM3, and UBASH3A, as well as AIF and BCL2 during human kidney development. Human fetal kidney tissue was stained with antibodies and analyzed by fluorescence microscopy and RT-PCR. Quantification of positive cells was assessed by calculation of area percentage and counting cells in nephron structures. Results showed statistically significant differences in the temporal expression patterns of the examined markers, depending on the investigated developmental stage. Limited but strong expression of CRKL was seen in developing kidneys, with increasing expression up to the period where the majority of nephrons are formed. Results also lead us to conclude that AIFM3 and AIF are important for promoting cell survival, but only AIFM3 is considered a CAKUT candidate gene due to the lack of AIF in nephron developmental structures. Our findings imply great importance of AIFM3 in energy production in nephrogenesis and tubular maturation. UBASH3A raw scores showed greater immunoreactivity in developing structures than mature ones which would point to a meaningful role in nephrogenesis. The fact that mRNA and proteins of CRKL, UBASH3A, and AIFM3 were detected in all phases of kidney development implies their role as renal development control genes.

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TULA‐family proteins: Jacks of many trades and then some

Cited by 15 publications

References 95 publications

Functional unknomics: closing the knowledge gap to accelerate biomedical research

Functional unknomics: closing the knowledge gap to accelerate biomedical research

Identifying Temporally Regulated Root Nodulation Biomarkers Using Time Series Gene Co-Expression Network Analysis

CRKL, AIFM3, AIF, BCL2, and UBASH3A during Human Kidney Development

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