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Mitochondrial DNA. Part B, Resources 2023The complete chloroplast genome sequence of (Bosch) Copel. was determined in the present study. The genome is 145,943 base pairs (bp) in length and comprised two...
The complete chloroplast genome sequence of (Bosch) Copel. was determined in the present study. The genome is 145,943 base pairs (bp) in length and comprised two inverted repeats (32,990 bp) between a large single copy (92,170 bp) and a small single copy (20,783 bp). It contains 88 coding genes, 8 rRNA genes, 34 tRNA genes, and 1 pseudogene of and the GC content is 37.6%. Molecular phylogenetic analysis based on the plastid genome sequences of related taxa strongly supported the monophyly of the family Hymenophyllaceae, and the genus was a sister group of . In addition, compared to two large deletions of 453 bp and 878 bp were found in the IGS regions of and rrn16-trnV-GAC of cp genome, respectively.
PubMed: 37521905
DOI: 10.1080/23802359.2023.2238936 -
Nucleic Acids Research Mar 2024Much insight has been gained on how stem cells maintain genomic integrity, but less attention has been paid to how they maintain their transcriptome. Here, we report...
Much insight has been gained on how stem cells maintain genomic integrity, but less attention has been paid to how they maintain their transcriptome. Here, we report that the PIWI protein SMEDWI-1 plays a role in the filtering of dysfunctional transcripts from the transcriptome of planarian stem cells. SMEDWI-1 accomplishes this through association with the ribosomes during the pioneer round of translation, and processing of poorly translated transcripts into piRNAs. This results in the removal of such transcripts from the cytoplasmic pool and at the same time creates a dynamic pool of small RNAs for post-transcriptional surveillance through the piRNA pathway. Loss of SMEDWI-1 results in elevated levels of several non-coding transcripts, including rRNAs, snRNAs and pseudogene mRNAs, while reducing levels of several coding transcripts. In the absence of SMEDWI-1, stem cell colonies are delayed in their expansion and a higher fraction of descendants exit the stem cell state, indicating that this transcriptomic sanitation mediated by SMEDWI-1 is essential to maintain stem cell health. This study presents a new model for the function of PIWI proteins in stem cell maintenance, that complements their role in transposon repression, and proposes a new biogenesis pathway for piRNAs in stem cells.
Topics: Argonaute Proteins; DNA Transposable Elements; Helminth Proteins; Piwi-Interacting RNA; Platyhelminths; Proteins; RNA Interference; RNA, Small Interfering; Stem Cells; Animals
PubMed: 38142432
DOI: 10.1093/nar/gkad1212 -
Cell Reports Mar 2024U1 small nuclear RNA (snRNA) is an abundant and evolutionarily conserved 164-nucleotide RNA species that functions in pre-mRNA splicing, and it is considered to be a...
U1 small nuclear RNA (snRNA) is an abundant and evolutionarily conserved 164-nucleotide RNA species that functions in pre-mRNA splicing, and it is considered to be a housekeeping non-coding RNA. However, the role of U1 snRNA in regulating host antiviral immunity remains largely unexplored. Here, we find that RNVU1-18, a U1 pseudogene, is significantly upregulated in the host infected with RNA viruses, including influenza and respiratory syncytial virus. Overexpression of U1 snRNA protects cells against RNA viruses, while knockdown of U1 snRNA leads to more viral burden in vitro and in vivo. Knockout of RNVU1-18 is sufficient to impair the type I interferon-dependent antiviral innate immunity. U1 snRNA is required to fully activate the retinoic acid-inducible gene I (RIG-I)-dependent antiviral signaling, since it interacts with tripartite motif 25 (TRIM25) and enhances the RIG-I-TRIM25 interaction to trigger K63-linked ubiquitination of RIG-I. Our study reveals the important role of housekeeping U1 snRNA in regulating host antiviral innate immunity and restricting RNA virus infection.
Topics: Transcription Factors; Ubiquitin-Protein Ligases; DEAD Box Protein 58; Immunity, Innate; RNA, Small Nuclear; Ubiquitination; Tripartite Motif Proteins
PubMed: 38483900
DOI: 10.1016/j.celrep.2024.113945 -
Clinical and Experimental Medicine Jan 2024Colorectal cancer (CRC) and gastric cancer (GC) are major contributors to cancer-related mortality worldwide. Despite advancements in understanding molecular mechanisms... (Review)
Review
Colorectal cancer (CRC) and gastric cancer (GC) are major contributors to cancer-related mortality worldwide. Despite advancements in understanding molecular mechanisms and improved drug treatments, the overall survival rate for patients remains unsatisfactory. Metastasis and drug resistance are major challenges contributing to the high mortality rate in both CRC and GC. Recent research has shed light on the role of long noncoding RNAs (lncRNAs) in the development and progression of these cancers. LncRNAs regulate gene expression through various mechanisms, including epigenetic modifications and interactions with microRNAs (miRNAs) and proteins. They can serve as miRNA precursors or pseudogenes, modulating gene expression at transcriptional and post-transcriptional levels. Additionally, circulating lncRNAs have emerged as non-invasive biomarkers for the diagnosis, prognosis, and prediction of drug therapy response in CRC and GC. This review explores the intricate relationship between lncRNAs and CRC/GC, encompassing their roles in cancer development, progression, and chemoresistance. Furthermore, it discusses the potential of lncRNAs as therapeutic targets in these malignancies. The interplay between lncRNAs, miRNAs, and tumor microenvironment is also highlighted, emphasizing their impact on the complexity of cancer biology. Understanding the regulatory landscape and molecular mechanisms governed by lncRNAs in CRC and GC is crucial for the development of effective diagnostic and prognostic biomarkers, as well as novel therapeutic strategies. This review provides a comprehensive overview of the current knowledge and paves the way for further exploration of lncRNAs as key players in the management of CRC and GC.
Topics: Humans; RNA, Long Noncoding; Prognosis; Stomach Neoplasms; MicroRNAs; Colorectal Neoplasms; Tumor Microenvironment
PubMed: 38294554
DOI: 10.1007/s10238-023-01260-5 -
BMC Biology Nov 2023Over evolutionary timescales, genomic loci can switch between functional and non-functional states through processes such as pseudogenization and de novo gene birth....
BACKGROUND
Over evolutionary timescales, genomic loci can switch between functional and non-functional states through processes such as pseudogenization and de novo gene birth. Particularly, de novo gene birth is a widespread process, and many examples continue to be discovered across diverse evolutionary lineages. However, the general mechanisms that lead to functionalization are poorly understood, and estimated rates of de novo gene birth remain contentious. Here, we address this problem within a model that takes into account mutations and structural variation, allowing us to estimate the likelihood of emergence of new functions at non-functional loci.
RESULTS
Assuming biologically reasonable mutation rates and mutational effects, we find that functionalization of non-genic loci requires the realization of strict conditions. This is in line with the observation that most de novo genes are localized to the vicinity of established genes. Our model also provides an explanation for the empirical observation that emerging proto-genes are often lost despite showing signs of adaptation.
CONCLUSIONS
Our work elucidates the properties of non-genic loci that make them fertile for adaptation, and our results offer mechanistic insights into the process of de novo gene birth.
Topics: Evolution, Molecular; Mutation; Biological Evolution
PubMed: 37957718
DOI: 10.1186/s12915-023-01745-5 -
Communications Biology Sep 2023Diverse members of early-diverging Mucoromycota, including mycorrhizal taxa and soil-associated Mortierellaceae, are known to harbor Mollicutes-related endobacteria...
Diverse members of early-diverging Mucoromycota, including mycorrhizal taxa and soil-associated Mortierellaceae, are known to harbor Mollicutes-related endobacteria (MRE). It has been hypothesized that MRE were acquired by a common ancestor and transmitted vertically. Alternatively, MRE endosymbionts could have invaded after the divergence of Mucoromycota lineages and subsequently spread to new hosts horizontally. To better understand the evolutionary history of MRE symbionts, we generated and analyzed four complete MRE genomes from two Mortierellaceae genera: Linnemannia (MRE-L) and Benniella (MRE-B). These genomes include the smallest known of fungal endosymbionts and showed signals of a tight relationship with hosts including a reduced functional capacity and genes transferred from fungal hosts to MRE. Phylogenetic reconstruction including nine MRE from mycorrhizal fungi revealed that MRE-B genomes are more closely related to MRE from Glomeromycotina than MRE-L from the same host family. We posit that reductions in genome size, GC content, pseudogene content, and repeat content in MRE-L may reflect a longer-term relationship with their fungal hosts. These data indicate Linnemannia and Benniella MRE were likely acquired independently after their fungal hosts diverged from a common ancestor. This work expands upon foundational knowledge on minimal genomes and provides insights into the evolution of bacterial endosymbionts.
Topics: Tenericutes; Phylogeny; Genomics; Mycorrhizae; Genome Size
PubMed: 37723238
DOI: 10.1038/s42003-023-05299-8 -
Intragenomic rDNA variation - the product of concerted evolution, mutation, or something in between?Heredity Sep 2023The classical model of concerted evolution states that hundreds to thousands of ribosomal DNA (rDNA) units undergo homogenization, making the multiple copies of the... (Review)
Review
The classical model of concerted evolution states that hundreds to thousands of ribosomal DNA (rDNA) units undergo homogenization, making the multiple copies of the individual units more uniform across the genome than would be expected given mutation frequencies and gene redundancy. While the universality of this over 50-year-old model has been confirmed in a range of organisms, advanced high throughput sequencing techniques have also revealed that rDNA homogenization in many organisms is partial and, in rare cases, even apparently failing. The potential underpinning processes leading to unexpected intragenomic variation have been discussed in a number of studies, but a comprehensive understanding remains to be determined. In this work, we summarize information on variation or polymorphisms in rDNAs across a wide range of taxa amongst animals, fungi, plants, and protists. We discuss the definition and description of concerted evolution and describe whether incomplete concerted evolution of rDNAs predominantly affects coding or non-coding regions of rDNA units and if it leads to the formation of pseudogenes or not. We also discuss the factors contributing to rDNA variation, such as interspecific hybridization, meiotic cycles, rDNA expression status, genome size, and the activity of effector genes involved in genetic recombination, epigenetic modifications, and DNA editing. Finally, we argue that a combination of approaches is needed to target genetic and epigenetic phenomena influencing incomplete concerted evolution, to give a comprehensive understanding of the evolution and functional consequences of intragenomic variation in rDNA.
Topics: Animals; DNA, Ribosomal; Genetic Variation; Mutation; Polymorphism, Genetic; Fungi; Evolution, Molecular; Phylogeny
PubMed: 37402824
DOI: 10.1038/s41437-023-00634-5 -
Nucleic Acids Research May 2024microRNAs (miRNAs) regulate nearly all physiological processes but our understanding of exactly how they function remains incomplete, particularly in the context of...
microRNAs (miRNAs) regulate nearly all physiological processes but our understanding of exactly how they function remains incomplete, particularly in the context of viral infections. Here, we adapt a biochemical method (CLEAR-CLIP) and analysis pipeline to identify targets of miRNAs in lung cells infected with Respiratory syncytial virus (RSV). We show that RSV binds directly to miR-26 and miR-27 through seed pairing and demonstrate that these miRNAs target distinct gene networks associated with cell cycle and metabolism (miR-27) and antiviral immunity (miR-26). Many of the targets are de-repressed upon infection and we show that the miR-27 targets most sensitive to miRNA inhibition are those associated with cell cycle. Finally, we demonstrate that high confidence chimeras map to long noncoding RNAs (lncRNAs) and pseudogenes in transcriptional regulatory regions. We validate that a proportion of miR-27 and Argonaute 2 (AGO2) is nuclear and identify a long non-coding RNA (lncRNA) as a miR-27 target that is linked to transcriptional regulation of nearby genes. This work expands the target networks of miR-26 and miR-27 to include direct interactions with RSV and lncRNAs and implicate these miRNAs in regulation of key genes that impact the viral life cycle associated with cell cycle, metabolism, and antiviral immunity.
Topics: Humans; Argonaute Proteins; Cell Cycle; Cell Line; Gene Expression Regulation; Gene Regulatory Networks; Host-Pathogen Interactions; MicroRNAs; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Syncytial Viruses; RNA, Long Noncoding
PubMed: 38412296
DOI: 10.1093/nar/gkae116 -
Heliyon Apr 2024Breast cancer (BC) remains the most common cancer among women, and novel post-surgical reconstruction techniques, including autologous fat transplantation, have emerged....
BACKGROUND
Breast cancer (BC) remains the most common cancer among women, and novel post-surgical reconstruction techniques, including autologous fat transplantation, have emerged. While Adipose-derived stem cells (ADSCs) are known to impact the viability of fat grafts, their influence on breast cancer progression remains unclear. This study aims to elucidate the genetic interplay between ADSCs and breast cancer, focusing on potential therapeutic targets.
METHODS
Using the GEO and TCGA databases, we pinpointed differentially expressed (DE) mRNAs, miRNAs, lncRNAs, and pseudogenes of ADSCs and BC. We performed functional enrichment analysis and constructed protein-protein interaction (PPI), RNA binding protein (RBP)-pseudogene-mRNA, and lncRNA-miRNA-transcription factor (TF)-gene networks. Our study delved into the correlation of AK4 expression with 33 different malignancies and examined its impact on prognostic outcomes across a pan-cancer cohort. Additionally, we scrutinized immune infiltration, microsatellite instability, and tumor mutational burden, and conducted single-cell analysis to further understand the implications of AK4 expression. We identified novel sample subtypes based on hub genes using the ConsensusClusterPlus package and examined their association with immune infiltration. The random forest algorithm was used to screen DE mRNAs between subtypes to validate the powerful prognostic prediction ability of the artificial neural network.
RESULTS
Our analysis identified 395 DE mRNAs, 3 DE miRNAs, 84 DE lncRNAs, and 26 DE pseudogenes associated with ADSCs and BC. Of these, 173 mRNAs were commonly regulated in both ADSCs and breast cancer, and 222 exhibited differential regulation. The PPI, RBP-pseudogene-mRNA, and lncRNA-miRNA-TF-gene networks suggested AK4 as a key regulator. Our findings support AK4 as a promising immune-related therapeutic target for a wide range of malignancies. We identified 14 characteristic genes based on the AK4-related cluster using the random forest algorithm. Our artificial neural network yielded excellent diagnostic performance in the testing cohort with AUC values of 0.994, 0.973, and 0.995, indicating its ability to distinguish between breast cancer and non-breast cancer cases.
CONCLUSIONS
Our research sheds light on the dual role of ADSCs in BC at the genetic level and identifies AK4 as a key protective mRNA in breast cancer. We found that AK4 significantly predicts cancer prognosis and immunotherapy, indicating its potential as a therapeutic target.
PubMed: 38560200
DOI: 10.1016/j.heliyon.2024.e27357 -
American Journal of Translational... 2023Although evidence regarding pituitary tumor-transforming 3, pseudogene (PTTG3P) involvement in human cancers has been acquired via human and animal model-based molecular...
BACKGROUND
Although evidence regarding pituitary tumor-transforming 3, pseudogene (PTTG3P) involvement in human cancers has been acquired via human and animal model-based molecular studies, there is a lack of pan-cancer analysis of this gene in human tumors.
METHODS
Tumor-causing effects of PTTG3P in 24 human tumors were explored using The Cancer Genome Atlas (TCGA) datasets from different bioinformatics databases and applying in silico tools such as The University of ALabama at Birmingham CANcer (UALCAN), Human Protein Atlas (HPA), Kaplan Meier (KM) plotter, cBioPortal, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Cytoscape, Database for Annotation, Visualization, and Integrated Discovery (DAVID), Tumor IMmune Estimation Resource (TIMER), and Comparative Toxicogenomics Database (CTD). Then, via in vitro experiments, including RNA sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq), expression and promoter methylation levels of PTTG3P were verified in cell lines.
RESULTS
The PTTG3P expression was overexpressed across 23 malignancies and its overexpression was further found significantly effecting the overall survival (OS) durations of the esophageal carcinoma (ESCA) and head and neck cancer (HNSC) patients. This important information helps us to understand that PTTG3P plays a significant role in the development and progression of ESCA and HNSC. As for PTTG3P functional mechanisms, this gene along with its other binding partners was significantly concentrated in "Oocyte meiosis", "Cell cycle", "Ubiquitin mediated proteolysis", and "Progesterone-mediated oocyte maturation". Moreover, ESCA and HNSC tissues having the higher expression of PTTG3P were found to have lower promoter methylation levels of PTTG3P and higher CD8+ T immune cells level. Additionally, PTTG3P expression-regulatory drugs were also explored in the current manuscript for designing appropriate treatment strategies for ESCA and HNSC with respect to PTTG3P expression.
CONCLUSION
Our pan-cancer based findings provided a comprehensive account of the oncogenic role and utilization of PTTG3P as a novel molecular biomarker of ESCA and HNSC.
PubMed: 37692950
DOI: No ID Found