VELCRO-IP RNA-seq reveals ribosome expansion segment function in translation genome-wide

AbstractGlucocorticoid hormones (GCs) — acting through hippocampal mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) — are critical to physiological regulation and behavioural adaptation. We conducted genome-wide MR and GR ChIP-seq and Ribo-Zero RNA-seq studies on rat hippocampus to elucidate MR- and GR-regulated genes under circadian variation or acute stress. In a subset of genes, these physiological conditions resulted in enhanced MR and/or GR binding to DNA sequences and associated transcriptional changes. Binding of MR at a substantial number of sites however remained unchanged. MR and GR binding occur at overlapping as well as distinct loci. Moreover, although the GC response element (GRE) was the predominant motif, the transcription factor recognition site composition within MR and GR binding peaks show marked differences. Pathway analysis uncovered that MR and GR regulate a substantial number of genes involved in synaptic/neuro-plasticity, cell morphology and development, behavior, and neuropsychiatric disorders. We find that MR, not GR, is the predominant receptor binding to >50 ciliary genes; and that MR function is linked to neuronal differentiation and ciliogenesis in human fetal neuronal progenitor cells. These results show that hippocampal MRs and GRs constitutively and dynamically regulate genomic activities underpinning neuronal plasticity and behavioral adaptation to changing environments.

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SPLICE-q: a Python tool for genome-wide quantification of splicing efficiency

BMC Bioinformatics ◽

10.1186/s12859-021-04282-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Verônica R. de Melo Costa ◽

Julianus Pfeuffer ◽

Annita Louloupi ◽

Ulf A. V. Ørom ◽

Rosario M. Piro

Keyword(s):

Gene Expression ◽

Cancer Progression ◽

Time Course ◽

Progressive Increase ◽

Rna Seq ◽

Transcript Processing ◽

Aberrant Transcript ◽

Genome Wide ◽

Splicing Efficiency ◽

Nascent Rna

Abstract Background Introns are generally removed from primary transcripts to form mature RNA molecules in a post-transcriptional process called splicing. An efficient splicing of primary transcripts is an essential step in gene expression and its misregulation is related to numerous human diseases. Thus, to better understand the dynamics of this process and the perturbations that might be caused by aberrant transcript processing it is important to quantify splicing efficiency. Results Here, we introduce SPLICE-q, a fast and user-friendly Python tool for genome-wide SPLICing Efficiency quantification. It supports studies focusing on the implications of splicing efficiency in transcript processing dynamics. SPLICE-q uses aligned reads from strand-specific RNA-seq to quantify splicing efficiency for each intron individually and allows the user to select different levels of restrictiveness concerning the introns’ overlap with other genomic elements such as exons of other genes. We applied SPLICE-q to globally assess the dynamics of intron excision in yeast and human nascent RNA-seq. We also show its application using total RNA-seq from a patient-matched prostate cancer sample. Conclusions Our analyses illustrate that SPLICE-q is suitable to detect a progressive increase of splicing efficiency throughout a time course of nascent RNA-seq and it might be useful when it comes to understanding cancer progression beyond mere gene expression levels. SPLICE-q is available at: https://github.com/vrmelo/SPLICE-q

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Genome-Wide Identification and Characterization of Hsf and Hsp Gene Families and Gene Expression Analysis under Heat Stress in Eggplant (Solanum melongema L.)

Horticulturae ◽

10.3390/horticulturae7060149 ◽

2021 ◽

Vol 7 (6) ◽

pp. 149

Author(s):

Chao Gong ◽

Qiangqiang Pang ◽

Zhiliang Li ◽

Zhenxing Li ◽

Riyuan Chen ◽

...

Keyword(s):

Heat Stress ◽

Gene Families ◽

High Temperature Stress ◽

Pcr Analysis ◽

Rna Seq ◽

Genome Wide ◽

Motif Composition ◽

Hsp Genes ◽

Identification And Characterization

Under high temperature stress, a large number of proteins in plant cells will be denatured and inactivated. Meanwhile Hsfs and Hsps will be quickly induced to remove denatured proteins, so as to avoid programmed cell death, thus enhancing the thermotolerance of plants. Here, a comprehensive identification and analysis of the Hsf and Hsp gene families in eggplant under heat stress was performed. A total of 24 Hsf-like genes and 117 Hsp-like genes were identified from the eggplant genome using the interolog from Arabidopsis. The gene structure and motif composition of Hsf and Hsp genes were relatively conserved in each subfamily in eggplant. RNA-seq data and qRT-PCR analysis showed that the expressions of most eggplant Hsf and Hsp genes were increased upon exposure to heat stress, especially in thermotolerant line. The comprehensive analysis indicated that different sets of SmHsps genes were involved downstream of particular SmHsfs genes. These results provided a basis for revealing the roles of SmHsps and SmHsp for thermotolerance in eggplant, which may potentially be useful for understanding the thermotolerance mechanism involving SmHsps and SmHsp in eggplant.

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FOXO1 mitigates the SMAD3/FOXL2C134W transcriptomic effect in a model of human adult granulosa cell tumor

Journal of Translational Medicine ◽

10.1186/s12967-021-02754-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Christian Secchi ◽

Paola Benaglio ◽

Francesca Mulas ◽

Martina Belli ◽

Dwayne Stupack ◽

...

Keyword(s):

Granulosa Cell ◽

Chromatin Remodeling ◽

Granulosa Cell Tumor ◽

Cell Tumor ◽

Rna Seq ◽

Pathogenic Role ◽

Rare Type ◽

Cellular Models ◽

Genome Wide

Abstract Background Adult granulosa cell tumor (aGCT) is a rare type of stromal cell malignant cancer of the ovary characterized by elevated estrogen levels. aGCTs ubiquitously harbor a somatic mutation in FOXL2 gene, Cys134Trp (c.402C < G); however, the general molecular effect of this mutation and its putative pathogenic role in aGCT tumorigenesis is not completely understood. We previously studied the role of FOXL2C134W, its partner SMAD3 and its antagonist FOXO1 in cellular models of aGCT. Methods In this work, seeking more comprehensive profiling of FOXL2C134W transcriptomic effects, we performed an RNA-seq analysis comparing the effect of FOXL2WT/SMAD3 and FOXL2C134W/SMAD3 overexpression in an established human GC line (HGrC1), which is not luteinized, and bears normal alleles of FOXL2. Results Our data shows that FOXL2C134W/SMAD3 overexpression alters the expression of 717 genes. These genes include known and novel FOXL2 targets (TGFB2, SMARCA4, HSPG2, MKI67, NFKBIA) and are enriched for neoplastic pathways (Proteoglycans in Cancer, Chromatin remodeling, Apoptosis, Tissue Morphogenesis, Tyrosine Kinase Receptors). We additionally expressed the FOXL2 antagonistic Forkhead protein, FOXO1. Surprisingly, overexpression of FOXO1 mitigated 40% of the altered genome-wide effects specifically related to FOXL2C134W, suggesting it can be a new target for aGCT treatment. Conclusions Our transcriptomic data provide novel insights into potential genes (FOXO1 regulated) that could be used as biomarkers of efficacy in aGCT patients.

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Extremes of age are associated with differences in the expression of selected pattern recognition receptor genes and ACE2, the receptor for SARS-CoV-2: implications for the epidemiology of COVID-19 disease

BMC Medical Genomics ◽

10.1186/s12920-021-00970-7 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Stephen W. Bickler ◽

David M. Cauvi ◽

Kathleen M. Fisch ◽

James M. Prieto ◽

Alicia G. Sykes ◽

...

Keyword(s):

Pattern Recognition ◽

Dermal Fibroblasts ◽

Pattern Recognition Receptor ◽

Human Dermal Fibroblasts ◽

Rna Seq ◽

Large Dataset ◽

Genome Wide ◽

The Individual ◽

Recognition Receptor

Abstract Background Older aged adults and those with pre-existing conditions are at highest risk for severe COVID-19 associated outcomes. Methods Using a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts (GSE113957) we investigated whether age affects the expression of pattern recognition receptor (PRR) genes and ACE2, the receptor for SARS-CoV-2. Results Extremes of age are associated with increased expression of selected PRR genes, ACE2 and four genes that encode proteins that have been shown to interact with SAR2-CoV-2 proteins. Conclusions Assessment of PRR expression might provide a strategy for stratifying the risk of severe COVID-19 disease at both the individual and population levels.

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Genome-wide analysis of long non-coding RNAs (lncRNAs) in two contrasting soybean genotypes subjected to phosphate starvation

BMC Genomics ◽

10.1186/s12864-021-07750-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jinyu Zhang ◽

Huanqing Xu ◽

Yuming Yang ◽

Xiangqian Zhang ◽

Zhongwen Huang ◽

...

Keyword(s):

Growth And Yield ◽

Biological Processes ◽

Rna Seq ◽

Plant Growth And Development ◽

P Deficiency ◽

Genome Wide ◽

Low Phosphorus ◽

Soybean Genotypes ◽

Non Coding Rnas ◽

Sensitive Genotype

Abstract Background Phosphorus (P) is essential for plant growth and development, and low-phosphorus (LP) stress is a major factor limiting the growth and yield of soybean. Long noncoding RNAs (lncRNAs) have recently been reported to be key regulators in the responses of plants to stress conditions, but the mechanism through which LP stress mediates the biogenesis of lncRNAs in soybean remains unclear. Results In this study, to explore the response mechanisms of lncRNAs to LP stress, we used the roots of two representative soybean genotypes that present opposite responses to P deficiency, namely, a P-sensitive genotype (Bogao) and a P-tolerant genotype (NN94156), for the construction of RNA sequencing (RNA-seq) libraries. In total, 4,166 novel lncRNAs, including 525 differentially expressed (DE) lncRNAs, were identified from the two genotypes at different P levels. GO and KEGG analyses indicated that numerous DE lncRNAs might be involved in diverse biological processes related to phosphate, such as lipid metabolic processes, catalytic activity, cell membrane formation, signal transduction, and nitrogen fixation. Moreover, lncRNA-mRNA-miRNA and lncRNA-mRNA networks were constructed, and the results identified several promising lncRNAs that might be highly valuable for further analysis of the mechanism underlying the response of soybean to LP stress. Conclusions These results revealed that LP stress can significantly alter the genome-wide profiles of lncRNAs, particularly those of the P-sensitive genotype Bogao. Our findings increase the understanding of and provide new insights into the function of lncRNAs in the responses of soybean to P stress.

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