Tight regulation of gene expression is important for the survival of , a model bacterium of extreme stress resistance. Few studies have examined the use of regulatory RNAs as a possible contributing mechanism to ionizing radiation (IR) resistance, despite their proffered efficient and dynamic gene expression regulation under IR stress. This work presents a transcriptome-based approach for the identification of stress-responsive regulatory 5' untranslated region (5'-UTR) elements in R1 that can be broadly applied to other bacteria. Using this platform and an fluorescence screen, we uncovered the presence of a radiation-responsive regulatory motif in the 5' UTR of the DNA gyrase subunit A gene. Additional screens under HO-induced oxidative stress revealed the specificity of the response of this element to IR stress. Further examination of the sequence revealed a regulatory motif of the radiation and desiccation response (RDR) in the 5' UTR that is necessary for the recovery of from high doses of IR. Furthermore, we suggest that it is the preservation of predicted RNA structure, in addition to DNA sequence consensus of the motif, that permits this important regulatory ability. is an extremely stress-resistant bacterium capable of tolerating up to 3,000 times more ionizing radiation than human cells. As an integral part of the stress response mechanism of this organism, we suspect that it maintains stringent control of gene expression. However, understanding of its regulatory pathways remains incomplete to date. Untranslated RNA elements have been demonstrated to play crucial roles in gene regulation throughout bacteria. In this work, we focus on searching for and characterizing responsive RNA elements under radiation stress and propose that multiple levels of gene regulation work simultaneously to enable this organism to efficiently recover from exposure to ionizing radiation. The model we propose serves as a generic template to investigate similar mechanisms of gene regulation under stress that have likely evolved in other bacterial species.
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http://dx.doi.org/10.1128/AEM.00039-17 | DOI Listing |
Brief Bioinform
November 2024
Institute for Molecular Bioscience, The University of Queensland, 306 Carmody Road, St Lucia, Brisbane, QLD 4072, Australia.
Regulatory genes are critical determinants of cellular responses in development and disease, but standard RNA sequencing (RNA-seq) analysis workflows, such as differential expression analysis, have significant limitations in revealing the regulatory basis of cell identity and function. To address this challenge, we present the TRIAGE R package, a toolkit specifically designed to analyze regulatory elements in both bulk and single-cell RNA-seq datasets. The package is built upon TRIAGE methods, which leverage consortium-level H3K27me3 data to enrich for cell-type-specific regulatory regions.
View Article and Find Full Text PDFBrief Bioinform
November 2024
State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou, Xuanwu District, Nanjing 210096, China.
Spatial transcriptomics technologies have been extensively applied in biological research, enabling the study of transcriptome while preserving the spatial context of tissues. Paired with spatial transcriptomics data, platforms often provide histology and (or) chromatin images, which capture cellular morphology and chromatin organization. Additionally, single-cell RNA sequencing (scRNA-seq) data from matching tissues often accompany spatial data, offering a transcriptome-wide gene expression profile of individual cells.
View Article and Find Full Text PDFBrief Bioinform
November 2024
School of Electrical Engineering and Computer Science, Gwangju Institute of Science and Technology (GIST), Buk-gu, Gwangju 61005, Republic of Korea.
Combination therapies have emerged as a promising approach for treating complex diseases, particularly cancer. However, predicting the efficacy and safety profiles of these therapies remains a significant challenge, primarily because of the complex interactions among drugs and their wide-ranging effects. To address this issue, we introduce DD-PRiSM (Decomposition of Drug-Pair Response into Synergy and Monotherapy effect), a deep-learning pipeline that predicts the effects of combination therapy.
View Article and Find Full Text PDFBrief Bioinform
November 2024
Department of Electronic Engineering, Tsinghua University, 100084 Beijing, China.
Single-cell multi-omics techniques, which enable the simultaneous measurement of multiple modalities such as RNA gene expression and Assay for Transposase-Accessible Chromatin (ATAC) within individual cells, have become a powerful tool for deciphering the intricate complexity of cellular systems. Most current methods rely on motif databases to establish cross-modality relationships between genes from RNA-seq data and peaks from ATAC-seq data. However, these approaches are constrained by incomplete database coverage, particularly for novel or poorly characterized relationships.
View Article and Find Full Text PDFMol Biol Rep
January 2025
Goat Genetics and Breeding Division, ICAR-Central Institute for Research On Goats, Makhdoom, Farah, Mathura, 281 122, Uttar Pradesh, India.
Background: Extracellular matrix (ECM) proteins play a crucial role in regulating the biological properties of adherent cells. For cryopreserved fibroblasts, a favourable ECM environment can help restore their natural morphology and function more rapidly, minimizing post-thaw stress responses.
Methods And Results: This study explored the functional responses of cryopreserved enriched caprine adult dermal fibroblast (cadFibroblast) cells to structural [collagen-IV and rat tail collagen (RTC)] and adhesion ECM proteins (laminin, fibronectin, and vitronectin) under in vitro culture conditions.
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