scholarly journals Import of Non-Coding RNAs into Human Mitochondria: A Critical Review and Emerging Approaches

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 286 ◽  
Author(s):  
Damien Jeandard ◽  
Anna Smirnova ◽  
Ivan Tarassov ◽  
Eric Barrey ◽  
Alexandre Smirnov ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Nuclear Genome ◽  
Genetic System ◽  
Mitochondrial Import ◽  
In Situ Techniques ◽  
Genome Wide ◽  
Experimental Approaches ◽  
Non Coding Rnas ◽  
Analyze Data

Mitochondria harbor their own genetic system, yet critically depend on the import of a number of nuclear-encoded macromolecules to ensure their expression. In all eukaryotes, selected non-coding RNAs produced from the nuclear genome are partially redirected into the mitochondria, where they participate in gene expression. Therefore, the mitochondrial RNome represents an intricate mixture of the intrinsic transcriptome and the extrinsic RNA importome. In this review, we summarize and critically analyze data on the nuclear-encoded transcripts detected in human mitochondria and outline the proposed molecular mechanisms of their mitochondrial import. Special attention is given to the various experimental approaches used to study the mitochondrial RNome, including some recently developed genome-wide and in situ techniques.

scholarly journals Spatial analysis of ligand-receptor interactions in skin cancer at genome-wide and single-cell resolution

2020 ◽  
Author(s):  
M Tran ◽  
S Yoon ◽  
ST Min ◽  
S Andersen ◽  
K Devitt ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Cell Interactions ◽  
Genome Wide ◽  
Receptor Interactions ◽  
Cell Cell

AbstractThe ability to study cancer-immune cell communication across the whole tumor section without tissue dissociation is important to understand molecular mechanisms of cancer immunotherapy and drug targets. Current experimental methods such as immunohistochemistry allow researchers to investigate a small number of cells or a limited number of ligand-receptor pairs at tissue scale with limited cellular resolution. In this work, we developed a powerful experimental and analytical pipeline that allows for the genome-wide discovery and targeted validation of cellular communication. By profiling thousands of genes, spatial transcriptomic and single-cell RNA sequencing data show genes that are possibly involved in interactions. The expression of the candidate genes could be visualized by single-molecule in situ hybridization and droplet digital PCR. We developed a computational pipeline called STRISH that enables us to quantitatively model cell-cell interactions by automatically scanning for local expression of RNAscope data to recapitulate an interaction landscape across the whole tissue. Furthermore, we showed the strong correlation of microscopic RNAscope imaging data analyzed by STRISH with the gene expression values measured by droplet digital PCR. We validated the unique ability of this approach to discover new cell-cell interactions in situ through analysis of two types of cancer, basal cell carcinoma and squamous cell carcinoma. We expect that the approach described here will help to discover and validate ligand receptor interactions in different biological contexts such as immune-cancer cell interactions within a tumor.

scholarly journals Genome-wide identification and characterization of long non-coding RNAs conferring resistance to Colletotrichum gloeosporioides in walnut (Juglans regia)

2020 ◽  
Author(s):  
Shan Feng ◽  
Hongcheng Fang ◽  
Xia Liu ◽  
Yuhui Dong ◽  
Qingpeng Wang ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Plant Disease Resistance ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Colletotrichum Gloeosporioides ◽  
Juglans Regia ◽  
Bioinformatic Analysis ◽  
Genome Wide ◽  
Phenylpropanoid Biosynthesis ◽  
Non Coding Rnas

Abstract Background: Walnut anthracnose caused by Colletotrichum gloeosporioides (Penz.) Penz. and Sacc. is an important walnut production problem in China. Although the long non-coding RNAs (lncRNAs) are important for plant disease resistance , the molecular mechanisms underlying resistance to C. gloeosporioides in walnut remain poorly understood.Results: The anthracnose-resistant F26 fruits from the B26 clone and the anthracnose-susceptible F423 fruits from the 4-23 clone of walnut were used as the test materials. Specifically, we performed a comparative transcriptome analysis of F26 and F423 fruit bracts to identify differentially expressed LncRNAs (DELs) at five time-points (tissues at 0 hpi, pathological tissues at 24 hpi, 48 hpi, 72 hpi, and distal uninoculated tissues at 120 hpi). Compared with F423, a total of 14525 DELs were identified, including 10645 upregulated lncRNAs and 3846 downregulated lncRNAs in F26. The number of upregulated lncRNAs in F26 compared to in F423 was significantly higher at the early stages of C. gloeosporioides infection. A total of 5 modules related to disease resistance were screened by WGCNA and the target genes of lncRNAs were obtained. Bioinformatic analysis showed that the target genes of upregulated lncRNAs were enriched in immune-related processes during the infection of C. gloeosporioides, such as activation of innate immune response, defense response to bacterium, incompatible interaction and immune system process, and enriched in plant hormone signal transduction, phenylpropanoid biosynthesis and other pathways. And 124 known target genes for 96 hub lncRNAs were predicted, including 10 known resistance genes. The expression of 5 lncRNAs and 5 target genes was confirmed by qPCR, which was consistent with the RNA-seq data.Conclusions: The results of this study provide the basis for future functional characterizations of lncRNAs regarding the C. gloeosporioides resistance of walnut fruit bracts.

scholarly journals Long Non-Coding RNAs as Molecular Signatures for Canine B-Cell Lymphoma Characterization

2019 ◽  
Vol 5 (3) ◽  
pp. 47 ◽  
Author(s):  
Luciano Cascione ◽  
Luca Giudice ◽  
Serena Ferraresso ◽  
Laura Marconato ◽  
Diana Giannuzzi ◽  
...  
Keyword(s):  
B Cell ◽  
High Performance ◽  
Molecular Mechanisms ◽  
Cell Lymphoma ◽  
Transcriptome Assembly ◽  
B Cell Lymphoma ◽  
Genome Wide ◽  
Animal Tumor ◽  
Non Coding Rnas ◽  
Diagnosis Therapy

Background: Diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) and follicular lymphoma (FL) are the most common B-cell lymphomas (BCL) in dogs. Recent investigations have demonstrated overlaps of these histotypes with the human counterparts, including clinical presentation, biologic behavior, tumor genetics, and treatment response. The molecular mechanisms that underlie canine BCL are still unknown and new studies to improve diagnosis, therapy, and the utilization of canine species as spontaneous animal tumor models are undeniably needed. Recent work using human DLBCL transcriptomes has suggested that long non-coding RNAs (lncRNAs) play a key role in lymphoma pathogenesis and pinpointed a restricted number of lncRNAs as potential targets for further studies. Results: To expand the knowledge of non-coding molecules involved in canine BCL, we used transcriptomes obtained from a cohort of 62 dogs with newly-diagnosed multicentric DLBCL, MZL and FL that had undergone complete staging work-up and were treated with chemotherapy or chemo-immunotherapy. We developed a customized R pipeline performing a transcriptome assembly by multiple algorithms to uncover novel lncRNAs, and delineate genome-wide expression of unannotated and annotated lncRNAs. Our pipeline also included a new package for high performance system biology analysis, which detects high-scoring network biological neighborhoods to identify functional modules. Moreover, our customized pipeline quantified the expression of novel and annotated lncRNAs, allowing us to subtype DLBCLs into two main groups. The DLBCL subtypes showed statistically different survivals, indicating the potential use of lncRNAs as prognostic biomarkers in future studies. Conclusions: In this manuscript, we describe the methodology used to identify lncRNAs that differentiate B-cell lymphoma subtypes and we interpreted the biological and clinical values of the results. We inferred the potential functions of lncRNAs to obtain a comprehensive and integrative insight that highlights their impact in this neoplasm.

scholarly journals CRISPR Tools for Physiology and Cell State Changes: Potential of Transcriptional Engineering and Epigenome Editing

2021 ◽  
Vol 101 (1) ◽  
pp. 177-211
Author(s):  
Christopher T. Breunig ◽  
Anna Köferle ◽  
Andrea M. Neuner ◽  
Maximilian F. Wiesbeck ◽  
Valentin Baumann ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
New Technologies ◽  
Epigenome Editing ◽  
Dna Targeting ◽  
Genome Wide ◽  
Transcriptional Engineering ◽  
Genome Wide Data ◽  
Experimental Approaches ◽  
State Changes

Given the large amount of genome-wide data that have been collected during the last decades, a good understanding of how and why cells change during development, homeostasis, and disease might be expected. Unfortunately, the opposite is true; triggers that cause cellular state changes remain elusive, and the underlying molecular mechanisms are poorly understood. Although genes with the potential to influence cell states are known, the historic dependency on methods that manipulate gene expression outside the endogenous chromatin context has prevented us from understanding how cells organize, interpret, and protect cellular programs. Fortunately, recent methodological innovations are now providing options to answer these outstanding questions, by allowing to target and manipulate individual genomic and epigenomic loci. In particular, three experimental approaches are now feasible due to DNA targeting tools, namely, activation and/or repression of master transcription factors in their endogenous chromatin context; targeting transcription factors to endogenous, alternative, or inaccessible sites; and finally, functional manipulation of the chromatin context. In this article, we discuss the molecular basis of DNA targeting tools and review the potential of these new technologies before we summarize how these have already been used for the manipulation of cellular states and hypothesize about future applications.

scholarly journals Sexual reproduction contributes to the evolution of resistance breaking isolates of the spinach pathogen Peronospora effusa

2021 ◽  
Author(s):  
Petros Skiadas ◽  
Joel Klein ◽  
Thomas Quiroz Monnens ◽  
Joyce Elberse ◽  
Ronnie de Jonge ◽  
...  
Keyword(s):  
Sexual Reproduction ◽  
Molecular Mechanisms ◽  
Nuclear Genome ◽  
Resistance Breeding ◽  
Systematic Analysis ◽  
Genome Wide ◽  
Diversity Assessment ◽  
Long Read ◽  
Evolution Of Resistance ◽  
Important Disease

Peronospora effusa causes downy mildew, the economically most important disease of cultivated spinach worldwide. To date, 19 P. effusa races have been denominated based on their capacity to break spinach resistances, but their genetic diversity and the evolutionary processes that contribute to race emergence are unknown. Here, we performed the first systematic analysis of P. effusa races showing that those emerge by both asexual and sexual reproduction. Specifically, we studied the diversity of 26 P. effusa isolates from 16 denominated races based on mitochondrial and nuclear comparative genomics. Mitochondrial genomes based on long-read sequencing coupled with diversity assessment based on short-read sequencing uncovered two mitochondrial haplogroups, each with distinct genome organization. Nuclear genome-wide comparisons of the 26 isolates revealed that ten isolates from six races could clearly be divided into three asexually evolving groups, in concordance with their mitochondrial phylogeny. The remaining isolates showed signals of reticulated evolution and discordance between nuclear and mitochondrial phylogenies, suggesting that these evolved through sexual reproduction. Increased understanding of this pathogen's reproductive modes will provide the framework for future studies into the molecular mechanisms underlying race emergence and into the P. effusa-spinach interaction, thus assisting in sustainable production of spinach through knowledge-driven resistance breeding.

scholarly journals Genome-wide identification and characterization of long non-coding RNAs conferring resistance to Colletotrichum gloeosporioides in walnut (Juglans regia)

2020 ◽  
Author(s):  
Shan Feng ◽  
Hongcheng Fang ◽  
Xia Liu ◽  
Yuhui Dong ◽  
Qingpeng Wang ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Plant Disease Resistance ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Colletotrichum Gloeosporioides ◽  
Juglans Regia ◽  
Bioinformatic Analysis ◽  
Genome Wide ◽  
Phenylpropanoid Biosynthesis ◽  
Non Coding Rnas

Abstract Background: Walnut anthracnose caused by Colletotrichum gloeosporioides (Penz.) Penz. and Sacc. is an important walnut production problem in China. Although the long non-coding RNAs (lncRNAs) are important for plant disease resistance , the molecular mechanisms underlying resistance to C. gloeosporioides in walnut remain poorly understood.Results: The anthracnose-resistant F26 fruits from the B26 clone and the anthracnose-susceptible F423 fruits from the 4-23 clone of walnut were used as the test materials. Specifically, we performed a comparative transcriptome analysis of F26 and F423 fruit bracts to identify differentially expressed LncRNAs (DELs) at five time-points (tissues at 0 hpi, pathological tissues at 24 hpi, 48 hpi, 72 hpi, and distal uninoculated tissues at 120 hpi). Compared with F423, a total of 14525 DELs were identified, including 10645 upregulated lncRNAs and 3846 downregulated lncRNAs in F26. The number of upregulated lncRNAs in F26 compared to in F423 was significantly higher at the early stages of C. gloeosporioides infection. A total of 5 modules related to disease resistance were screened by WGCNA and the target genes of lncRNAs were obtained. Bioinformatic analysis showed that the target genes of upregulated lncRNAs were enriched in immune-related processes during the infection of C. gloeosporioides, such as activation of innate immune response, defense response to bacterium, incompatible interaction and immune system process, and enriched in plant hormone signal transduction, phenylpropanoid biosynthesis and other pathways. And 124 known target genes for 96 hub lncRNAs were predicted, including 10 known resistance genes. The expression of 5 lncRNAs and 5 target genes was confirmed by qPCR, which was consistent with the RNA-seq data.Conclusions: The results of this study provide the basis for future functional characterizations of lncRNAs regarding the C. gloeosporioides resistance of walnut fruit bracts.

scholarly journals Non-Coding RNAs and Splicing Activity in Testicular Germ Cell Tumors

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 736
Author(s):  
Marco Barchi ◽  
Pamela Bielli ◽  
Susanna Dolci ◽  
Pellegrino Rossi ◽  
Paola Grimaldi
Keyword(s):  
Germ Cell ◽  
Molecular Mechanisms ◽  
Splice Variants ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Protein Coding ◽  
Chemotherapeutic Response ◽  
Genome Wide ◽  
Non Coding Rnas

Testicular germ cell tumors (TGCTs) are the most common tumors in adolescent and young men. Recently, genome-wide studies have made it possible to progress in understanding the molecular mechanisms underlying the development of tumors. It is becoming increasingly clear that aberrant regulation of RNA metabolism can drive tumorigenesis and influence chemotherapeutic response. Notably, the expression of non-coding RNAs as well as specific splice variants is deeply deregulated in human cancers. Since these cancer-related RNA species are considered promising diagnostic, prognostic and therapeutic targets, understanding their function in cancer development is becoming a major challenge. Here, we summarize how the different expression of RNA species repertoire, including non-coding RNAs and protein-coding splicing variants, impacts on TGCTs’ onset and progression and sustains therapeutic resistance. Finally, the role of transcription-associated R-loop misregulation in the maintenance of genomic stability in TGCTs is also discussed.

scholarly journals The molecular mechanisms of LncRNA-correlated PKM2 in cancer metabolism

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Ting Tao ◽  
Shiyuan Wu ◽  
Zheng Sun ◽  
Wei Ma ◽  
Sichun Zhou ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metabolism ◽  
Metabolic Reprogramming ◽  
Functional Studies ◽  
Genome Wide ◽  
Non Coding Rnas ◽  
Cancer Tissues ◽  
Rate Limiting ◽  
Important Marker

Abstract Reprogrammed metabolism is an important hallmark of cancer cells. Pyruvate kinase (PK) is one of the major rate-limiting enzymes in glucose metabolism. The M2 isoform of PK (PKM2), is considered to be an important marker of metabolic reprogramming and one of the key enzymes. Recently, through the continuous development of genome-wide analysis and functional studies, accumulating evidence has demonstrated that long non-coding RNAs (LncRNAs) play vital regulatory roles in cancer progression by acting as either potential oncogenes or tumor suppressors. Furthermore, several studies have shown that up-regulation of PKM2 in cancer tissues is associated with LncRNAs expression and patient survival. Thus, scientists have begun to unveil the mechanism of LncRNA-associated PKM2 in cancer metabolic progression. Based on these novel findings, in this mini-review, we summarize the detailed molecular mechanisms of LncRNA related to PKM2 in cancer metabolism. We expect that this work will promote a better understanding of the molecular mechanisms of PKM2, and provide a profound potential for targeting PKM2 to treat tumors.

scholarly journals Multidimensional Mechanistic Spectrum of Long Non-coding RNAs in Heart Development and Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Lei Han ◽  
Lei Yang
Keyword(s):  
Heart Development ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Regulatory Mechanism ◽  
Mrna Translation ◽  
Genome Wide ◽  
Key Factor ◽  
Non Coding Rnas ◽  
And Function ◽  
Human Heart Disease

With the large-scale genome-wide sequencing, long non-coding RNAs (lncRNAs) have been found to compose of a large portion of the human transcriptome. Recent studies demonstrated the multidimensional functions of lncRNAs in heart development and disease. The subcellular localization of lncRNA is considered as a key factor that determines lncRNA function. Cytosolic lncRNAs mainly regulate mRNA stability, mRNA translation, miRNA processing and function, whereas nuclear lncRNAs epigenetically regulate chromatin remodeling, structure, and gene transcription. In this review, we summarize the molecular mechanisms of cytosolic and nuclear lncRNAs in heart development and disease separately, and emphasize the recent progress to dictate the crosstalk of cytosolic and nuclear lncRNAs in orchestrating the same biological process. Given the low evolutionary conservation of most lncRNAs, deeper understanding of human lncRNA will uncover a new layer of human regulatory mechanism underlying heart development and disease, and benefit the future clinical treatment for human heart disease.

scholarly journals Genome-wide identification and characterization of long non-coding RNAs conferring resistance to Colletotrichum gloeosporioides in walnut (Juglans regia)

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shan Feng ◽  
Hongcheng Fang ◽  
Xia Liu ◽  
Yuhui Dong ◽  
Qingpeng Wang ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Plant Disease Resistance ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Colletotrichum Gloeosporioides ◽  
Juglans Regia ◽  
Bioinformatic Analysis ◽  
Genome Wide ◽  
Phenylpropanoid Biosynthesis ◽  
Non Coding Rnas

Abstract Background Walnut anthracnose caused by Colletotrichum gloeosporioides (Penz.) Penz. and Sacc. is an important walnut production problem in China. Although the long non-coding RNAs (lncRNAs) are important for plant disease resistance, the molecular mechanisms underlying resistance to C. gloeosporioides in walnut remain poorly understood. Results The anthracnose-resistant F26 fruits from the B26 clone and the anthracnose-susceptible F423 fruits from the 4–23 clone of walnut were used as the test materials. Specifically, we performed a comparative transcriptome analysis of F26 and F423 fruit bracts to identify differentially expressed LncRNAs (DELs) at five time-points (tissues at 0 hpi, pathological tissues at 24 hpi, 48 hpi, 72 hpi, and distal uninoculated tissues at 120 hpi). Compared with F423, a total of 14,525 DELs were identified, including 10,645 upregulated lncRNAs and 3846 downregulated lncRNAs in F26. The number of upregulated lncRNAs in F26 compared to in F423 was significantly higher at the early stages of C. gloeosporioides infection. A total of 5 modules related to disease resistance were screened by WGCNA and the target genes of lncRNAs were obtained. Bioinformatic analysis showed that the target genes of upregulated lncRNAs were enriched in immune-related processes during the infection of C. gloeosporioides, such as activation of innate immune response, defense response to bacterium, incompatible interaction and immune system process, and enriched in plant hormone signal transduction, phenylpropanoid biosynthesis and other pathways. And 124 known target genes for 96 hub lncRNAs were predicted, including 10 known resistance genes. The expression of 5 lncRNAs and 5 target genes was confirmed by qPCR, which was consistent with the RNA-seq data. Conclusions The results of this study provide the basis for future functional characterizations of lncRNAs regarding the C. gloeosporioides resistance of walnut fruit bracts.

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