scholarly journals The small noncoding RNA sr8384 determines solvent synthesis and cell growth in industrial solventogenic clostridia

2019 ◽  
Author(s):  
Yunpeng Yang ◽  
Nannan Lang ◽  
Huan Zhang ◽  
Lu Zhang ◽  
Changsheng Chai ◽  
...  
Keyword(s):  
Cell Growth ◽  
Clostridium Acetobutylicum ◽  
Noncoding Rna ◽  
Large Scale ◽  
Target Genes ◽  
Biological Processes ◽  
Small Noncoding Rna ◽  
Small Noncoding Rnas ◽  
Solventogenic Clostridia

ABSTRACTSmall noncoding RNAs (sncRNAs) are crucial regulatory molecules in organisms and are well known not only for their roles in the control of diverse essential biological processes but also for their value in genetic modification. However, to date, in gram-positive anaerobic solventogenic clostridia (which are a group of important industrial bacteria with exceptional substrate and product diversity), sncRNAs remain minimally explored, leading to a lack of detailed understanding regarding these important molecules and their use as targets for genetic improvement. Here, we performed large-scale phenotypic screens of a transposon-mediated mutant library ofClostridium acetobutylicum, a typical solventogenic clostridial species, and discovered a novel sncRNA (sr8384) that functions as a determinant positive regulator of growth and solvent synthesis. Comparative transcriptomic data combined with genetic and biochemical analyses revealed that sr8384 acts as a pleiotropic regulator and controls multiple targets that are associated with crucial biological processes, through direct or indirect interactions. Notably, modulation of the expression level of either sr8384 or its core target genes significantly increased the growth rate, solvent titer and productivity of the cells, indicating the importance of sr8384-mediated regulatory network inC. acetobutylicum. Furthermore, a homolog of sr8384 was discovered and proven to be functional in another importantClostridiumspecies,C. beijerinckii, suggesting the potential broad role of this sncRNA in clostridia. Our work showcases a previously unknown potent and complex role of sncRNAs in clostridia, providing new opportunities for understanding and engineering these anaerobes, including pathogenicClostridiumspecies.IMPORTANCEThe discovery of sncRNAs as new resources for functional studies and strain modifications are promising strategies in microorganisms. However, these crucial regulatory molecules have hardly been explored in industrially important solventogenic clostridia. Here, we identified sr8384 as a novel determinant sncRNA controlling cellular performance of solventogenicClostridium acetobutylicumand performed detailed functional analysis, which is the most in-depth study of sncRNAs in clostridia to date. We reveal the pleiotropic function of sr8384 and its multiple direct and indirect crucial targets, which represents a valuable source for understanding and optimizing this anaerobe. Of note, manipulation of these targets leads to improved cell growth and solvent synthesis. Our findings provide a new perspective for future studies on regulatory sncRNAs in clostridia.

scholarly journals The Small RNA sr8384 Is a Crucial Regulator of Cell Growth in Solventogenic Clostridia

2020 ◽  
Vol 86 (13) ◽  
Author(s):  
Yunpeng Yang ◽  
Huan Zhang ◽  
Nannan Lang ◽  
Lu Zhang ◽  
Changsheng Chai ◽  
...  
Keyword(s):  
Cell Growth ◽  
Clostridium Acetobutylicum ◽  
Large Scale ◽  
Biological Processes ◽  
Content Type ◽  
Functional Studies ◽  
Biochemical Analyses ◽  
Solventogenic Clostridia

ABSTRACT Small RNAs (sRNAs) are crucial regulatory molecules in organisms and are well-known not only for their roles in the control of diverse crucial biological processes but also for their value in regulation rewiring. However, to date, in Gram-positive anaerobic solventogenic clostridia (a group of important industrial bacteria with exceptional substrate and product diversity), sRNAs remain minimally explored, and thus there is a lack of detailed understanding regarding these important molecules and their use as targets for genetic improvement. Here, we performed large-scale phenotypic screens of a transposon-mediated mutant library of Clostridium acetobutylicum, a typical solventogenic clostridial species, and discovered a novel sRNA (sr8384) that functions as a crucial regulator of cell growth. Comparative transcriptomic data combined with genetic and biochemical analyses revealed that sr8384 acts as a pleiotropic regulator and controls multiple targets that are associated with crucial biological processes through direct or indirect interactions. Notably, the in vivo expression level of sr8384 determined the cell growth rate, thereby affecting the solvent titer and productivity. These findings indicate the importance of the sr8384-mediated regulatory network in C. acetobutylicum. Furthermore, a homolog of sr8384 was discovered and proven to be functional in another important Clostridium species, C. beijerinckii, suggesting the potential broad role of this sRNA in clostridia. Our work showcases a previously unknown potent and complex role of sRNAs in clostridia, providing new opportunities for understanding and engineering these anaerobes. IMPORTANCE The uses of sRNAs as new resources for functional studies and strain modifications are promising strategies in microorganisms. However, these crucial regulatory molecules have hardly been explored in industrially important solventogenic clostridia. Here, we identified sr8384 as a novel determinant sRNA controlling the cell growth of solventogenic Clostridium acetobutylicum. Based on a detailed functional analysis, we further reveal the pleiotropic function of sr8384 and its multiple direct and indirect crucial targets, which represents a valuable source for understanding and optimizing this anaerobe. Of note, manipulation of this sRNA achieves improved cell growth and solvent synthesis. Our findings provide a new perspective for future studies on regulatory sRNAs in clostridia.

scholarly journals The emerging role of microRNAs in bone remodeling and its therapeutic implications for osteoporosis

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Qianyun Feng ◽  
Sheng Zheng ◽  
Jia Zheng
Keyword(s):  
Bone Remodeling ◽  
Noncoding Rna ◽  
Target Genes ◽  
Epigenetic Modification ◽  
Therapeutic Implications ◽  
Small Noncoding Rna ◽  
Genetic And Environmental Factors ◽  
Underlying Mechanisms ◽  
Post Transcriptional Regulation

Osteoporosis, a common and multifactorial disease, is influenced by genetic factors and environments. However, the pathogenesis of osteoporosis has not been fully elucidated yet. Recently, emerging evidence suggests that epigenetic modifications may be the underlying mechanisms that link genetic and environmental factors with increased risks of osteoporosis and bone fracture. MicroRNA (miRNA), a major category of small noncoding RNA with 20–22 bases in length, is recognized as one important epigenetic modification. It can mediate post-transcriptional regulation of target genes with cell differentiation and apoptosis. In this review, we aimed to profile the role of miRNA in bone remodeling and its therapeutic implications for osteoporosis. A deeper insight into the role of miRNA in bone remodeling and osteoporosis can provide unique opportunities to develop a novel diagnostic and therapeutic approach of osteoporosis.

scholarly journals Modulated Autophagy by MicroRNAs in Osteoarthritis Chondrocytes

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yinghao Yu ◽  
Jijun Zhao
Keyword(s):  
Target Genes ◽  
Cartilage Degradation ◽  
Joint Disease ◽  
Future Research ◽  
Biological Processes ◽  
Small Noncoding Rnas ◽  
New Directions ◽  
Osteoarthritis Chondrocytes ◽  
Cell Signaling Pathways

Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage regression. The etiology of OA is diverse, the exact pathogenesis of which remains unclear. Autophagy is a conserved maintenance mechanism in eukaryotic cells. Dysfunction of chondrocyte autophagy is regarded as a crucial pathogenesis of cartilage degradation in OA. MircoRNAs (miRNAs) are a category of small noncoding RNAs, acting as posttranscriptional modulators that regulate biological processes and cell signaling pathways via target genes. A series of miRNAs are involved in the progression of chondrocyte autophagy and are connected with numerous factors and pathways. This article focuses on the mechanisms of chondrocyte autophagy in OA and reviews the role of miRNA in their modulation. Potentially relevant miRNAs are also discussed in order to provide new directions for future research and improve our understanding of the autophagic network of miRNAs.

scholarly journals Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational epigenetic inheritance of multiple diseases

2021 ◽  
Author(s):  
Xin Yin ◽  
Azhar Anwar ◽  
Yanbo Wang ◽  
Huanhuan Hu ◽  
Gaoli Liang ◽  
...  
Keyword(s):  
Environmental Exposure ◽  
Noncoding Rna ◽  
Relevant Literature ◽  
Epigenetic Inheritance ◽  
Rna Regulation ◽  
Small Noncoding Rna ◽  
Small Noncoding Rnas ◽  
Male Line ◽  
The Veil

AbstractStudies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.

scholarly journals Emerging multifaceted roles of BAP1 complexes in biological processes

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Aileen Patricia Szczepanski ◽  
Lu Wang
Keyword(s):  
Transcriptional Repression ◽  
Target Genes ◽  
Regulatory Mechanisms ◽  
Biological Processes ◽  
Multiprotein Complex ◽  
Downstream Target ◽  
Evolutionarily Conserved ◽  
Complex Forms ◽  
Polycomb Repressive Complex 1

AbstractHistone H2AK119 mono-ubiquitination (H2AK119Ub) is a relatively abundant histone modification, mainly catalyzed by the Polycomb Repressive Complex 1 (PRC1) to regulate Polycomb-mediated transcriptional repression of downstream target genes. Consequently, H2AK119Ub can also be dynamically reversed by the BAP1 complex, an evolutionarily conserved multiprotein complex that functions as a general transcriptional activator. In previous studies, it has been reported that the BAP1 complex consists of important biological roles in development, metabolism, and cancer. However, identifying the BAP1 complex’s regulatory mechanisms remains to be elucidated due to its various complex forms and its ability to target non-histone substrates. In this review, we will summarize recent findings that have contributed to the diverse functional role of the BAP1 complex and further discuss the potential in targeting BAP1 for therapeutic use.

The role of microRNA-21 in the onset and progression of cancer

2021 ◽  
Author(s):  
Ashutosh Singh ◽  
Ashutosh Kumar Singh ◽  
Rajanish Giri ◽  
Dhruv Kumar ◽  
Rohit Sharma ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Tumor Suppressor Genes ◽  
Noncoding Rna ◽  
Early Cancer ◽  
Cancer Resistance ◽  
Aberrant Expression ◽  
Small Noncoding Rna ◽  
Expression Of Genes ◽  
Oncogenic Property

MicroRNAs (miRNAs), a class of small noncoding RNA, posttranscriptionally regulate the expression of genes. Aberrant expression of miRNA is reported in various types of cancer. Since the first report of oncomiR-21 involvement in the glioma, its upregulation was reported in multiple cancers and was allied with high oncogenic property. In addition to the downregulation of tumor suppressor genes, the miR-21 is also associated with cancer resistance to various chemotherapy. The recent research is appraising miR-21 as a promising cancer target and biomarker for early cancer detection. In this review, we briefly explain the biogenesis and regulation of miR-21 in cancer cells. Additionally, the review features the assorted genes/pathways regulated by the miR-21 in various cancer and cancer stem cells.

scholarly journals Curcumin inhibits cancer progression through regulating expression of microRNAs

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769168 ◽  
Author(s):  
Siying Zhou ◽  
Sijie Zhang ◽  
Hongyu Shen ◽  
Wei Chen ◽  
Hanzi Xu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Target Genes ◽  
Therapeutic Potential ◽  
Tumor Biology ◽  
Multiple Cancer ◽  
Small Noncoding Rna ◽  
Cancer Agent ◽  
Regulation Of Cell Cycle

Curcumin, a major yellow pigment and spice in turmeric and curry, is a powerful anti-cancer agent. The anti-tumor activities of curcumin include inhibition of tumor proliferation, angiogenesis, invasion and metastasis, induction of tumor apoptosis, increase of chemotherapy sensitivity, and regulation of cell cycle and cancer stem cell, indicating that curcumin maybe a strong therapeutic potential through modulating various cancer progression. It has been reported that microRNAs as small noncoding RNA molecules are related to cancer progression, which can be regulated by curcumin. Dysregulated microRNAs play vital roles in tumor biology via regulating expressions of target genes and then influencing multiple cancer-related signaling pathways. In this review, we focused on the inhibition effect of curcumin on various cancer progression by regulating expression of multiple microRNAs. Curcumin-induced dysregulation of microRNAs may activate or inactivate a set of signaling pathways, such as Akt, Bcl-2, PTEN, p53, Notch, and Erbb signaling pathways. A better understanding of the relation between curcumin and microRNAs may provide a potential therapeutic target for various cancers.

scholarly journals Hypoxia and HIF Signaling: One Axis with Divergent Effects

2020 ◽  
Vol 21 (16) ◽  
pp. 5611 ◽  
Author(s):  
Chiara Corrado ◽  
Simona Fontana
Keyword(s):  
Cellular Response ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Biological Processes ◽  
Oxygen Homeostasis ◽  
Tissue Responses ◽  
Liver And Kidney ◽  
Heterodimeric Complex ◽  
Complex Activities

The correct concentration of oxygen in all tissues is a hallmark of cellular wellness, and the negative regulation of oxygen homeostasis is able to affect the cells and tissues of the whole organism. The cellular response to hypoxia is characterized by the activation of multiple genes involved in many biological processes. Among them, hypoxia-inducible factor (HIF) represents the master regulator of the hypoxia response. The active heterodimeric complex HIF α/β, binding to hypoxia-responsive elements (HREs), determines the induction of at least 100 target genes to restore tissue homeostasis. A growing body of evidence demonstrates that hypoxia signaling can act by generating contrasting responses in cells and tissues. Here, this dual and controversial role of hypoxia and the HIF signaling pathway is discussed, with particular reference to the effects induced on the complex activities of the immune system and on mechanisms determining cell and tissue responses after an injury in both acute and chronic human diseases related to the heart, lung, liver, and kidney.

MicroRNA: Potential biomarker and target of therapy in acute lung injury

2020 ◽  
Vol 39 (11) ◽  
pp. 1429-1442
Author(s):  
Z-F Jiang ◽  
L Zhang ◽  
J Shen
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Respiratory Diseases ◽  
Current Evidence ◽  
Biological Processes ◽  
Fatal Disease ◽  
Small Noncoding Rnas ◽  
Potential Biomarker ◽  
Indirect Injury

MicroRNAs (miRNAs) are small noncoding RNAs stretching over 18–22 nucleotides and considered to be modifiers of many respiratory diseases. They are highly evolutionary conserved and have been implicated in several biological processes, including cell proliferation, apoptosis, differentiation, among others. Acute lung injury (ALI) is a fatal disease commonly caused by direct or indirect injury factors and has a high mortality rate in intensive care unit. Changes in expression of several types of miRNAs have been reported in patients with ALI. Some miRNAs suppress cellular injury and accelerate the recovery of ALI by targeting specific molecules and decreasing excessive immune response. For this reason, miRNAs are proposed as potential biomarkers for ALI and as therapeutic targets for this disease. This review summarizes current evidence supporting the role of miRNAs in ALI.

Sign in / Sign up

Export Citation Format

Share Document