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Article: Editorial: Non-coding RNA elements as regulators of host-pathogen interactions.

Gama-Carvalho, Margarida / Tran, Nham

2024 Volume 15, Page(s) 1374636

Language	English
Publishing date	2024-03-05
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2024.1374636
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Small non-coding RNAs encoded by RNA viruses: old controversies and new lessons from the COVID-19 pandemic.

Ruivinho, Carolina / Gama-Carvalho, Margarida

Frontiers in genetics

2023 Volume 14, Page(s) 1216890

Abstract: The recurring outbreaks caused by emerging RNA viruses have fostered an increased interest in the research of the mechanisms that regulate viral life cycles and the pathological outcomes associated with infections. Although interactions at the protein ... ...

Abstract	The recurring outbreaks caused by emerging RNA viruses have fostered an increased interest in the research of the mechanisms that regulate viral life cycles and the pathological outcomes associated with infections. Although interactions at the protein level are well-studied, interactions mediated by RNA molecules are less explored. RNA viruses can encode small non-coding RNAs molecules (sncRNAs), including viral miRNAs (v-miRNAs), that play important roles in modulating host immune responses and viral replication by targeting viral or host transcripts. Starting from the analysis of public databases compiling the known repertoire of viral ncRNA molecules and the evolution of publications and research interests on this topic in the wake of the COVID-19 pandemic, we provide an updated view on the current knowledge on viral sncRNAs, with a focus on v-miRNAs encoded by RNA viruses, and their mechanisms of action. We also discuss the potential of these molecules as diagnostic and prognostic biomarkers for viral infections and the development of antiviral therapies targeting v-miRNAs. This review emphasizes the importance of continued research efforts to characterize sncRNAs encoded by RNA viruses, identifies the most relevant pitfalls in the study of these molecules, and highlights the paradigm changes that have occurred in the last few years regarding their biogenesis, prevalence and functional relevance in the context of host-pathogen interactions.
Language	English
Publishing date	2023-06-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2023.1216890
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Network Approaches to Study Endogenous RNA Competition and Its Impact on Tissue-Specific microRNA Functions.

Marques, Tânia Monteiro / Gama-Carvalho, Margarida

Biomolecules

2022 Volume 12, Issue 2

Abstract: microRNAs are small non-coding RNAs that play a key role in regulating gene expression. These molecules exert their function through sequence complementarity with microRNA responsive elements and are typically located in the 3' untranslated region of ... ...

Abstract	microRNAs are small non-coding RNAs that play a key role in regulating gene expression. These molecules exert their function through sequence complementarity with microRNA responsive elements and are typically located in the 3' untranslated region of mRNAs, negatively regulating expression. Even though the relevant role of miRNA-dependent regulation is broadly recognized, the principles governing their ability to lead to specific functional outcomes in distinct cell types are still not well understood. In recent years, an intriguing hypothesis proposed that miRNA-responsive elements act as communication links between different RNA species, making the investigation of microRNA function even more complex than previously thought. The competing endogenous RNA hypothesis suggests the presence of a new level of regulation, whereby a specific RNA transcript can indirectly influence the abundance of other transcripts by limiting the availability of a common miRNA, acting as a "molecular sponge". Since this idea has been proposed, several studies have tried to pinpoint the interaction networks that have been established between different RNA species and whether they contribute to normal cell function and disease. The focus of this review is to highlight recent developments and achievements made towards the process of characterizing competing endogenous RNA networks and their role in cellular function.
MeSH term(s)	Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; MicroRNAs/genetics ; RNA, Long Noncoding/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
Chemical Substances	MicroRNAs ; RNA, Long Noncoding ; RNA, Messenger
Language	English
Publishing date	2022-02-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12020332
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Article ; Online: Therapeutic Metabolic Reprograming Using microRNAs: From Cancer to HIV Infection.

Gibson, Mark S / Noronha-Estima, Cláudia / Gama-Carvalho, Margarida

Genes

2022 Volume 13, Issue 2

Abstract: MicroRNAs (miRNAs) are crucial regulators of cellular processes, including metabolism. Attempts to use miRNAs as therapeutic agents are being explored in several areas, including the control of cancer progression. Recent evidence suggests fine tuning ... ...

Abstract	MicroRNAs (miRNAs) are crucial regulators of cellular processes, including metabolism. Attempts to use miRNAs as therapeutic agents are being explored in several areas, including the control of cancer progression. Recent evidence suggests fine tuning miRNA activity to reprogram tumor cell metabolism has enormous potential as an alternative treatment option. Indeed, cancer growth is known to be linked to profound metabolic changes. Likewise, the emerging field of immunometabolism is leading to a refined understanding of how immune cell proliferation and function is governed by glucose homeostasis. Different immune cell types are now known to have unique metabolic signatures that switch in response to a changing environment. T-cell subsets exhibit distinct metabolic profiles which underlie their alternative differentiation and phenotypic functions. Recent evidence shows that the susceptibility of CD4
MeSH term(s)	HIV Infections/genetics ; HIV Infections/therapy ; HIV-1/genetics ; Humans ; MicroRNAs/metabolism ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/therapy ; T-Lymphocytes/metabolism
Chemical Substances	MicroRNAs
Language	English
Publishing date	2022-01-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13020273
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Article: Therapeutic Metabolic Reprograming Using microRNAs: From Cancer to HIV Infection

Gibson, Mark S. / Noronha-Estima, Cláudia / Gama-Carvalho, Margarida

Genes. 2022 Jan. 29, v. 13, no. 2

2022

Abstract	MicroRNAs (miRNAs) are crucial regulators of cellular processes, including metabolism. Attempts to use miRNAs as therapeutic agents are being explored in several areas, including the control of cancer progression. Recent evidence suggests fine tuning miRNA activity to reprogram tumor cell metabolism has enormous potential as an alternative treatment option. Indeed, cancer growth is known to be linked to profound metabolic changes. Likewise, the emerging field of immunometabolism is leading to a refined understanding of how immune cell proliferation and function is governed by glucose homeostasis. Different immune cell types are now known to have unique metabolic signatures that switch in response to a changing environment. T-cell subsets exhibit distinct metabolic profiles which underlie their alternative differentiation and phenotypic functions. Recent evidence shows that the susceptibility of CD4⁺ T-cells to HIV infection is intimately linked to their metabolic activity, with many of the metabolic features of HIV-1-infected cells resembling those found in tumor cells. In this review, we discuss the use of miRNA modulation to achieve metabolic reprogramming for cancer therapy and explore the idea that the same approach may serve as an effective mechanism to restrict HIV replication and eliminate infected cells.
Keywords	HIV infections ; biochemical pathways ; cancer therapy ; cell proliferation ; glucose ; homeostasis ; metabolism ; microRNA ; neoplasm cells ; neoplasm progression ; neoplasms ; phenotype
Language	English
Dates of publication	2022-0129
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13020273
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Genomic Tackling of Human Satellite DNA: Breaking Barriers through Time.

Lopes, Mariana / Louzada, Sandra / Gama-Carvalho, Margarida / Chaves, Raquel

International journal of molecular sciences

2021 Volume 22, Issue 9

Abstract: Peri)centromeric repetitive sequences and, more specifically, satellite DNA (satDNA) sequences, constitute a major human genomic component. SatDNA sequences can vary on a large number of features, including nucleotide composition, complexity, and ... ...

Abstract	(Peri)centromeric repetitive sequences and, more specifically, satellite DNA (satDNA) sequences, constitute a major human genomic component. SatDNA sequences can vary on a large number of features, including nucleotide composition, complexity, and abundance. Several satDNA families have been identified and characterized in the human genome through time, albeit at different speeds. Human satDNA families present a high degree of sub-variability, leading to the definition of various subfamilies with different organization and clustered localization. Evolution of satDNA analysis has enabled the progressive characterization of satDNA features. Despite recent advances in the sequencing of centromeric arrays, comprehensive genomic studies to assess their variability are still required to provide accurate and proportional representation of satDNA (peri)centromeric/acrocentric short arm sequences. Approaches combining multiple techniques have been successfully applied and seem to be the path to follow for generating integrated knowledge in the promising field of human satDNA biology.
MeSH term(s)	DNA, Satellite/chemistry ; DNA, Satellite/genetics ; Evolution, Molecular ; Genome, Human ; Genomics/methods ; Genomics/trends ; Humans ; Sequence Analysis, DNA/methods ; Sequence Analysis, DNA/trends ; Time Factors
Chemical Substances	DNA, Satellite
Language	English
Publishing date	2021-04-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22094707
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Article: Biological interacting units identified in human protein networks reveal tissue-functional diversification and its impact on disease.

García-Vaquero, Marina L / Gama-Carvalho, Margarida / Pinto, Francisco R / De Las Rivas, Javier

Computational and structural biotechnology journal

2022 Volume 20, Page(s) 3764–3778

Abstract: Protein-protein interactions (PPI) play an essential role in the biological processes that occur in the cell. Therefore, the dissection of PPI networks becomes decisive to model functional coordination and predict pathological de-regulation. Cellular ... ...

Abstract	Protein-protein interactions (PPI) play an essential role in the biological processes that occur in the cell. Therefore, the dissection of PPI networks becomes decisive to model functional coordination and predict pathological de-regulation. Cellular networks are dynamic and proteins display varying roles depending on the tissue-interactomic context. Thus, the use of centrality measures in individual proteins fall short to dissect the functional properties of the cell. For this reason, there is a need for more comprehensive, relational, and context-specific ways to analyze the multiple actions of proteins in different cells and identify specific functional assemblies within global biomolecular networks. Under this framework, we define
Language	English
Publishing date	2022-07-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2022.07.006
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Article ; Online: Human Satellite 1A analysis provides evidence of pericentromeric transcription.

Lopes, Mariana / Louzada, Sandra / Ferreira, Daniela / Veríssimo, Gabriela / Eleutério, Daniel / Gama-Carvalho, Margarida / Chaves, Raquel

BMC biology

2023 Volume 21, Issue 1, Page(s) 28

Abstract: Background: Pericentromeric regions of human chromosomes are composed of tandem-repeated and highly organized sequences named satellite DNAs. Human classical satellite DNAs are classified into three families named HSat1, HSat2, and HSat3, which have ... ...

Abstract	Background: Pericentromeric regions of human chromosomes are composed of tandem-repeated and highly organized sequences named satellite DNAs. Human classical satellite DNAs are classified into three families named HSat1, HSat2, and HSat3, which have historically posed a challenge for the assembly of the human reference genome where they are misrepresented due to their repetitive nature. Although being known for a long time as the most AT-rich fraction of the human genome, classical satellite HSat1A has been disregarded in genomic and transcriptional studies, falling behind other human satellites in terms of functional knowledge. Here, we aim to characterize and provide an understanding on the biological relevance of HSat1A. Results: The path followed herein trails with HSat1A isolation and cloning, followed by in silico analysis. Monomer copy number and expression data was obtained in a wide variety of human cell lines, with greatly varying profiles in tumoral/non-tumoral samples. HSat1A was mapped in human chromosomes and applied in in situ transcriptional assays. Additionally, it was possible to observe the nuclear organization of HSat1A transcripts and further characterize them by 3' RACE-Seq. Size-varying polyadenylated HSat1A transcripts were detected, which possibly accounts for the intricate regulation of alternative polyadenylation. Conclusion: As far as we know, this work pioneers HSat1A transcription studies. With the emergence of new human genome assemblies, acrocentric pericentromeres are becoming relevant characters in disease and other biological contexts. HSat1A sequences and associated noncoding RNAs will most certainly prove significant in the future of HSat research.
MeSH term(s)	Humans ; DNA, Satellite/genetics ; Tandem Repeat Sequences ; RNA, Untranslated ; Genomics ; Genome, Human
Chemical Substances	DNA, Satellite ; RNA, Untranslated
Language	English
Publishing date	2023-02-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2133020-7
ISSN	1741-7007 ; 1741-7007
ISSN (online)	1741-7007
ISSN	1741-7007
DOI	10.1186/s12915-023-01521-5
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Article: Mutation-class dependent signatures outweigh disease-associated processes in cystic fibrosis cells.

Santos, Lúcia / Nascimento, Rui / Duarte, Aires / Railean, Violeta / Amaral, Margarida D / Harrison, Patrick T / Gama-Carvalho, Margarida / Farinha, Carlos M

Cell & bioscience

2023 Volume 13, Issue 1, Page(s) 26

Abstract: Background: The phenotypic heterogeneity observed in Cystic Fibrosis (CF) patients suggests the involvement of other genes, besides CFTR. Here, we combined transcriptome and proteome analysis to understand the global gene expression patterns associated ... ...

Abstract	Background: The phenotypic heterogeneity observed in Cystic Fibrosis (CF) patients suggests the involvement of other genes, besides CFTR. Here, we combined transcriptome and proteome analysis to understand the global gene expression patterns associated with five prototypical CFTR mutations. Results: Evaluation of differentially expressed genes and proteins unveiled common and mutation-specific changes revealing functional signatures that are much more associated with the specific molecular defects associated with each mutation than to the CFTR loss-of-function phenotype. The combination of both datasets revealed that mutation-specific detected translated-transcripts (Dtt) have a high level of consistency. Conclusions: This is the first combined transcriptomic and proteomic study focusing on prototypical CFTR mutations. Analysis of Dtt provides novel insight into the pathophysiology of CF, and the mechanisms through which each mutation class causes disease and will likely contribute to the identification of new therapeutic targets and/or biomarkers for CF.
Language	English
Publishing date	2023-02-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2593367-X
ISSN	2045-3701
ISSN	2045-3701
DOI	10.1186/s13578-023-00975-y
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Article ; Online: DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells via the mTOR signaling pathway.

García-Moreno, Juan F / Lacerda, Rafaela / da Costa, Paulo J / Pereira, Marcelo / Gama-Carvalho, Margarida / Matos, Paulo / Romão, Luísa

Cellular and molecular life sciences : CMLS

2023 Volume 80, Issue 7, Page(s) 185

Abstract: DIS3L2 degrades different types of RNAs in an exosome-independent manner including mRNAs and several types of non-coding RNAs. DIS3L2-mediated degradation is preceded by the addition of nontemplated uridines at the 3'end of its targets by the terminal ... ...

Abstract	DIS3L2 degrades different types of RNAs in an exosome-independent manner including mRNAs and several types of non-coding RNAs. DIS3L2-mediated degradation is preceded by the addition of nontemplated uridines at the 3'end of its targets by the terminal uridylyl transferases 4 and 7. Most of the literature that concerns DIS3L2 characterizes its involvement in several RNA degradation pathways, however, there is some evidence that its dysregulated activity may contribute to cancer development. In the present study, we characterize the role of DIS3L2 in human colorectal cancer (CRC). Using the public RNA datasets from The Cancer Genome Atlas (TCGA), we found higher DIS3L2 mRNA levels in CRC tissues versus normal colonic samples as well as worse prognosis in patients with high DIS3L2 expression. In addition, our RNA deep-sequencing data revealed that knockdown (KD) of DIS3L2 induces a strong transcriptomic disturbance in SW480 CRC cells. Moreover, gene ontology (GO) analysis of significant upregulated transcripts displays enrichment in mRNAs encoding proteins involved in cell cycle regulation and cancer-related pathways, which guided us to evaluate which specific hallmarks of cancer are differentially regulated by DIS3L2. To do so, we employed four CRC cell lines (HCT116, SW480, Caco-2 and HT-29) differing in their mutational background and oncogenicity. We demonstrate that depletion of DIS3L2 results in reduced cell viability of highly oncogenic SW480 and HCT116 CRC cells, but had little or no impact in the more differentiated Caco-2 and HT-29 cells. Remarkably, the mTOR signaling pathway, crucial for cell survival and growth, is downregulated after DIS3L2 KD, whereas AZGP1, an mTOR pathway inhibitor, is upregulated. Furthermore, our results indicate that depletion of DIS3L2 disturbs metastasis-associated properties, such as cell migration and invasion, only in highly oncogenic CRC cells. Our work reveals for the first time a role for DIS3L2 in sustaining CRC cell proliferation and provides evidence that this ribonuclease is required to support the viability and invasive behavior of dedifferentiated CRC cells.
MeSH term(s)	Humans ; Caco-2 Cells ; Cell Line, Tumor ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Signal Transduction/genetics ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; HCT116 Cells ; Cell Proliferation/genetics ; RNA, Messenger ; Cell Movement/genetics ; Ribonucleases/genetics ; Gene Expression Regulation, Neoplastic ; Exoribonucleases/genetics ; Exoribonucleases/metabolism
Chemical Substances	TOR Serine-Threonine Kinases (EC 2.7.11.1) ; RNA, Messenger ; Ribonucleases (EC 3.1.-) ; DIS3L2 protein, human (EC 3.1.-) ; Exoribonucleases (EC 3.1.-)
Language	English
Publishing date	2023-06-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-023-04833-5
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