Multilayer and MATR3-dependent regulation of mRNAs maintains pluripotency in human induced pluripotent stem cells

Pollini, Daniele; Loffredo, Rosa; Maniscalco, Federica; Cardano, Marina; Micaelli, Mariachiara; Bonomo, Isabelle; Licata, Nausicaa Valentina; Peroni, Daniele; Tomaszewska, Weronika; Rossi, Annalisa; Crippa, V.; Dassi, Erik; Viero, Gabriella; Quattrone, Alessandro; Poletti, Angelo; Conti, Luciano; Provenzani, Alessandro

doi:10.1016/j.isci.2021.102197

Cited by 16 publications

(18 citation statements)

References 71 publications

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“…2 ). Matrin 3 is an RNA/DNA-binding protein with multiple functions in gene expression regulation, including stabilizing target RNAs, supporting transcription factor activity, and modulating chromatin architecture [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

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An in silico pipeline approach uncovers a potentially intricate network involving spike SARS-CoV-2 RNA, RNA vaccines, host RNA-binding proteins (RBPs), and host miRNAs at the cellular level

Chetta

Tarsitano

Oro

et al. 2022

Journal of Genetic Engineering and Biotechnology

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Background In the last 2 years, we have been fighting against SARS-CoV-2 viral infection, which continues to claim victims all over the world. The entire scientific community has been mobilized in an attempt to stop and eradicate the infection. A well-known feature of RNA viruses is their high mutational rate, particularly in specific gene regions. The SARS-CoV-2 S protein is also affected by these changes, allowing viruses to adapt and spread more easily. The vaccines developed using mRNA coding protein S undoubtedly contributed to the “fight” against the COVID-19 pandemic even though the presence of new variants in the spike protein could result in protein conformational changes, which could affect vaccine immunogenicity and thus vaccine effectiveness. Results The study presents the findings of an in silico analysis using various bioinformatics tools finding conserved sequences inside SARS-CoV-2 S protein (encoding mRNA) same as in the vaccine RNA sequences that could be targeted by specific host RNA-binding proteins (RBPs). According to the results an interesting scenario emerges involving host RBPs competition and subtraction. The presence of viral RNA in cytoplasm could be a new tool in the virus’s armory, allowing it to improve its chances of survival by altering cell gene expression and thus interfering with host cell processes. In silico analysis was used also to evaluate the presence of similar human miRNA sequences within RBPs motifs that can modulate human RNA expression. Increased cytoplasmic availability of exogenous RNA fragments derived from RNA physiological degradation could potentially mimic the effect of host human miRNAs within the cell, causing modulation of the host cell network. Conclusions Our in silico analysis could aid in shedding light on the potential effects of exogenous RNA (i.e. viruses and vaccines), thereby improving our understanding of the cellular interactions between virus and host biomolecules. Finally, using the computational approach, it is possible to obtain a safety assessment of RNA-based vaccines as well as indications for use in specific clinical conditions.

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Section: Resultsmentioning

confidence: 99%

“…Reduced availability of the SRSF1 protein, which regulates autophagy activation, as well as SRSF7 and SRSF9, which induce apoptosis in colon and lung cancer cells by controlling apoptosis [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

An in silico pipeline approach uncovers a potentially intricate network involving spike SARS-CoV-2 RNA, RNA vaccines, host RNA-binding proteins (RBPs), and host miRNAs at the cellular level

Chetta

Tarsitano

Oro

et al. 2022

Journal of Genetic Engineering and Biotechnology

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“…METTL3 maintained pluripotency of porcine iPSCs by sustaining JAK2 and inhibiting SOCS3 expression, and activating STAT3/Klf4/Sox2 signal axis in an m 6 A-YTHDF1/2-dependent manner (Wu et al, 2019b; Figure 2A). MATR3 favored the pluripotency of iPSCs by regulating the transcriptional and translational efficiency of Nanog, Lin28a, and Oct4 (Pollini et al, 2021; Figure 2C). YTHDF2 was highly expressed in iPSCs and downregulated during neural differentiation.…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 99%

The Roles of RNA N6-Methyladenosine in Regulating Stem Cell Fate

Zhang

2021

Front. Cell Dev. Biol.

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RNA N6-methyladenosine (m6A) modification has important regulatory roles in determining cell fate. The reversible methylation process of adding and removing m6A marks is dynamically regulated by a fine-tuned coordination of many enzymes and binding proteins. Stem cells have self-renewal and pluripotent potential and show broad prospects in regenerative medicine and other fields. Stem cells have also been identified in cancer, which is linked to cancer metastasis, therapy resistance, and recurrence. Herein, we aimed to review the molecular mechanism that controls the reversible balance of m6A level in stem cells and the effect of m6A modification on the balance between pluripotency and differentiation. Additionally, we also elaborated the association between aberrant m6A modification and the maintenance of cancer stem cells in many cancers. Moreover, we discussed about the clinical implications of m6A modification in cancer stem cells for cancer diagnosis and therapy.

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“…For another, MATR3 was recruited on ribosomes to regulate the translation of various specific transcripts such as Nanog and Lin28a through direct binding to keep their stabilization. MATR3 deficiency hampered both the proliferation and differentiation of human iPSCs ( Pollini et al, 2021 ).…”

Section: The Role Of M 6 a In Induced Pluripotent ...mentioning

confidence: 99%

N6-Methyladenosine RNA Modification: A Potential Regulator of Stem Cell Proliferation and Differentiation

Wei

Zeng

Yang

et al. 2022

Front. Cell Dev. Biol.

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Stem cell transplantation (SCT) holds great promise for overcoming diseases by regenerating damaged cells, tissues and organs. The potential for self-renewal and differentiation is the key to SCT. RNA methylation, a dynamic and reversible epigenetic modification, is able to regulate the ability of stem cells to differentiate and regenerate. N6-methyladenosine (m6A) is the richest form of RNA methylation in eukaryotes and is regulated by three classes of proteins: methyltransferase complexes, demethylase complexes and m6A binding proteins. Through the coordination of these proteins, RNA methylation precisely modulates the expression of important target genes by affecting mRNA stability, translation, selective splicing, processing and microRNA maturation. In this review, we summarize the most recent findings on the regulation of m6A modification in embryonic stem cells, induced pluripotent stem cells and adult stem cells, hoping to provide new insights into improving SCT technology.

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Multilayer and MATR3-dependent regulation of mRNAs maintains pluripotency in human induced pluripotent stem cells

Cited by 16 publications

References 71 publications

An in silico pipeline approach uncovers a potentially intricate network involving spike SARS-CoV-2 RNA, RNA vaccines, host RNA-binding proteins (RBPs), and host miRNAs at the cellular level

An in silico pipeline approach uncovers a potentially intricate network involving spike SARS-CoV-2 RNA, RNA vaccines, host RNA-binding proteins (RBPs), and host miRNAs at the cellular level

The Roles of RNA N6-Methyladenosine in Regulating Stem Cell Fate

N6-Methyladenosine RNA Modification: A Potential Regulator of Stem Cell Proliferation and Differentiation

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