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Article: The RNA-Binding Function of Ribosomal Proteins and Ribosome Biogenesis Factors in Human Health and Disease.

Catalanotto, Caterina / Barbato, Christian / Cogoni, Carlo / Benelli, Dario

2023 Volume 11, Issue 11

Abstract: The ribosome is a macromolecular complex composed of RNA and proteins that interact through an integrated and interconnected network to preserve its ancient core activities. In this review, we emphasize the pivotal role played by RNA-binding proteins as ... ...

Abstract	The ribosome is a macromolecular complex composed of RNA and proteins that interact through an integrated and interconnected network to preserve its ancient core activities. In this review, we emphasize the pivotal role played by RNA-binding proteins as a driving force in the evolution of the current form of the ribosome, underscoring their importance in ensuring accurate protein synthesis. This category of proteins includes both ribosomal proteins and ribosome biogenesis factors. Impairment of their RNA-binding activity can also lead to ribosomopathies, which is a group of disorders characterized by defects in ribosome biogenesis that are detrimental to protein synthesis and cellular homeostasis. A comprehensive understanding of these intricate processes is essential for elucidating the mechanisms underlying the resulting diseases and advancing potential therapeutic interventions.
Language	English
Publishing date	2023-11-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11112969
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Article ; Online: Silencing of Ago-2 Interacting Protein SERBP1 Relieves KCC2 Repression by miR-92 in Neurons.

Barbato, Christian / Frisone, Paola / Braccini, Laura / D'Aguanno, Simona / Pieroni, Luisa / Ciotti, Maria Teresa / Catalanotto, Caterina / Cogoni, Carlo / Ruberti, Francesca

Cells

2022 Volume 11, Issue 6

Abstract: RNA-binding proteins (RBPs) play important roles in modulating miRNA-mediated mRNA target repression. Argonaute2 (Ago2) is an essential component of the RNA-induced silencing complex (RISC) that plays a central role in silencing mechanisms via small non- ... ...

Abstract	RNA-binding proteins (RBPs) play important roles in modulating miRNA-mediated mRNA target repression. Argonaute2 (Ago2) is an essential component of the RNA-induced silencing complex (RISC) that plays a central role in silencing mechanisms via small non-coding RNA molecules known as siRNAs and miRNAs. Small RNAs loaded into Argonaute proteins catalyze endoribonucleolytic cleavage of target RNAs or recruit factors responsible for translational silencing and mRNA target destabilization. In previous studies we have shown that KCC2, a neuronal Cl (-) extruding K (+) Cl (-) co-transporter 2, is regulated by miR-92 in neuronal cells. Searching for Ago2 partners by immunoprecipitation and LC-MS/MS analysis, we isolated among other proteins the Serpine mRNA binding protein 1 (SERBP1) from SH-SY5Y neuroblastoma cells. Exploring the role of SERBP1 in miRNA-mediated gene silencing in SH-SY5Y cells and primary hippocampal neurons, we demonstrated that SERBP1 silencing regulates KCC2 expression through the 3' untranslated region (UTR). In addition, we found that SERBP1 as well as Ago2/miR-92 complex bind to KCC2 3'UTR. Finally, we demonstrated the attenuation of miR-92-mediated repression of KCC2 3'UTR by SERBP1 silencing. These findings advance our knowledge regarding the miR-92-mediated modulation of KCC2 translation in neuronal cells and highlight SERBP1 as a key component of this gene regulation.
MeSH term(s)	3' Untranslated Regions ; Chromatography, Liquid ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Neurons/metabolism ; RNA, Messenger/genetics ; RNA-Induced Silencing Complex/genetics ; Symporters/genetics ; Tandem Mass Spectrometry
Chemical Substances	3' Untranslated Regions ; MicroRNAs ; RNA, Messenger ; RNA-Induced Silencing Complex ; Symporters
Language	English
Publishing date	2022-03-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11061052
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Article: YY1 Knockdown Relieves the Differentiation Block and Restores Apoptosis in AML Cells.

Noguera, Nelida Ines / Travaglini, Serena / Scalea, Stefania / Catalanotto, Caterina / Reale, Anna / Zampieri, Michele / Zaza, Alessandra / Ricciardi, Maria Rosaria / Angelini, Daniela Francesca / Tafuri, Agostino / Ottone, Tiziana / Voso, Maria Teresa / Zardo, Giuseppe

Cancers

2023 Volume 15, Issue 15

Abstract: In this study we analyzed the expression of Yin and Yang 1 protein (YY1), a member of the noncanonical PcG complexes, in AML patient samples and AML cell lines and the effect of YY1 downregulation on the AML differentiation block. Our results show that ... ...

Abstract	In this study we analyzed the expression of Yin and Yang 1 protein (YY1), a member of the noncanonical PcG complexes, in AML patient samples and AML cell lines and the effect of YY1 downregulation on the AML differentiation block. Our results show that YY1 is significantly overexpressed in AML patient samples and AML cell lines and that YY1 knockdown relieves the differentiation block. YY1 downregulation in two AML cell lines (HL-60 and OCI-AML3) and one AML patient sample restored the expression of members of the CEBP protein family, increased the expression of extrinsic growth factors/receptors and surface antigenic markers, induced morphological cell characteristics typical of myeloid differentiation, and sensitized cells to retinoic acid treatment and to apoptosis. Overall, our data show that YY1 is not a secondary regulator of myeloid differentiation but that, if overexpressed, it can play a predominant role in myeloid differentiation block.
Language	English
Publishing date	2023-08-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15154010
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Article ; Online: Inhibition of Eukaryotic Translation Initiation Factor 5A (eIF5A) Hypusination Suppress p53 Translation and Alters the Association of eIF5A to the Ribosomes.

Martella, Marianna / Catalanotto, Caterina / Talora, Claudio / La Teana, Anna / Londei, Paola / Benelli, Dario

International journal of molecular sciences

2020 Volume 21, Issue 13

Abstract: The eukaryotic translation initiation factor 5A (eIF5A) is an essential protein for the viability of the cells whose proposed function is to prevent the stalling of the ribosomes during translation elongation. eIF5A activity requires a unique and ... ...

Abstract	The eukaryotic translation initiation factor 5A (eIF5A) is an essential protein for the viability of the cells whose proposed function is to prevent the stalling of the ribosomes during translation elongation. eIF5A activity requires a unique and functionally essential post-translational modification, the change of a lysine to hypusine. eIF5A is recognized as a promoter of cell proliferation, but it has also been suggested to induce apoptosis. To date, the precise molecular mechanism through which eIF5A affects these processes remains elusive. In the present study, we explored whether eIF5A is involved in controlling the stress-induced expression of the key cellular regulator p53. Our results show that treatment of HCT-116 colon cancer cells with the deoxyhypusine (DHS) inhibitor N1-guanyl-1,7-diamineheptane (GC7) caused both inhibition of eIF5A hypusination and a significant reduction of p53 expression in UV-treated cells, and that eIF5A controls p53 expression at the level of protein synthesis. Furthermore, we show that treatment with GC7 followed by UV-induced stress counteracts the pro-apoptotic process triggered by p53 up-regulation. More in general, the importance of eIF5A in the cellular stress response is illustrated by the finding that exposure to UV light promotes the binding of eIF5A to the ribosomes, whereas UV treatment complemented by the presence of GC7 inhibits such binding, allowing a decrease of de novo synthesis of p53 protein.
MeSH term(s)	Apoptosis ; Cell Proliferation ; Colonic Neoplasms/genetics ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Lysine/analogs & derivatives ; Lysine/chemistry ; Peptide Initiation Factors/chemistry ; Peptide Initiation Factors/genetics ; Peptide Initiation Factors/metabolism ; Protein Biosynthesis ; Protein Processing, Post-Translational ; RNA-Binding Proteins/chemistry ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Ribosomes/metabolism ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Eukaryotic Translation Initiation Factor 5A
Chemical Substances	Peptide Initiation Factors ; RNA-Binding Proteins ; TP53 protein, human ; Tumor Suppressor Protein p53 ; hypusine (3874VXF092) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2020-06-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21134583
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Article ; Online: MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions.

Catalanotto, Caterina / Cogoni, Carlo / Zardo, Giuseppe

International journal of molecular sciences

2016 Volume 17, Issue 10

Abstract: The finding that small non-coding RNAs (ncRNAs) are able to control gene expression in a sequence specific manner has had a massive impact on biology. Recent improvements in high throughput sequencing and computational prediction methods have allowed the ...

Abstract	The finding that small non-coding RNAs (ncRNAs) are able to control gene expression in a sequence specific manner has had a massive impact on biology. Recent improvements in high throughput sequencing and computational prediction methods have allowed the discovery and classification of several types of ncRNAs. Based on their precursor structures, biogenesis pathways and modes of action, ncRNAs are classified as small interfering RNAs (siRNAs), microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), endogenous small interfering RNAs (endo-siRNAs or esiRNAs), promoter associate RNAs (pRNAs), small nucleolar RNAs (snoRNAs) and sno-derived RNAs. Among these, miRNAs appear as important cytoplasmic regulators of gene expression. miRNAs act as post-transcriptional regulators of their messenger RNA (mRNA) targets via mRNA degradation and/or translational repression. However, it is becoming evident that miRNAs also have specific nuclear functions. Among these, the most studied and debated activity is the miRNA-guided transcriptional control of gene expression. Although available data detail quite precisely the effectors of this activity, the mechanisms by which miRNAs identify their gene targets to control transcription are still a matter of debate. Here, we focus on nuclear functions of miRNAs and on alternative mechanisms of target recognition, at the promoter lavel, by miRNAs in carrying out transcriptional gene silencing.
MeSH term(s)	Alternative Splicing ; Animals ; Cell Nucleolus/genetics ; Cell Nucleolus/metabolism ; Cytoplasm/genetics ; Cytoplasm/metabolism ; Gene Expression Regulation ; Humans ; MicroRNAs/analysis ; MicroRNAs/genetics ; MicroRNAs/metabolism ; RNA Transport ; Transcriptome
Chemical Substances	MicroRNAs
Language	English
Publishing date	2016-10-13
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/ijms17101712
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Article ; Online: Inhibition of Eukaryotic Translation Initiation Factor 5A (eIF5A) Hypusination Suppress p53 Translation and Alters the Association of eIF5A to the Ribosomes

Marianna Martella / Caterina Catalanotto / Claudio Talora / Anna La Teana / Paola Londei / Dario Benelli

International Journal of Molecular Sciences, Vol 21, Iss 4583, p

2020 Volume 4583

Abstract	The eukaryotic translation initiation factor 5A (eIF5A) is an essential protein for the viability of the cells whose proposed function is to prevent the stalling of the ribosomes during translation elongation. eIF5A activity requires a unique and functionally essential post-translational modification, the change of a lysine to hypusine. eIF5A is recognized as a promoter of cell proliferation, but it has also been suggested to induce apoptosis. To date, the precise molecular mechanism through which eIF5A affects these processes remains elusive. In the present study, we explored whether eIF5A is involved in controlling the stress-induced expression of the key cellular regulator p53. Our results show that treatment of HCT-116 colon cancer cells with the deoxyhypusine (DHS) inhibitor N1-guanyl-1,7-diamineheptane (GC7) caused both inhibition of eIF5A hypusination and a significant reduction of p53 expression in UV-treated cells, and that eIF5A controls p53 expression at the level of protein synthesis. Furthermore, we show that treatment with GC7 followed by UV-induced stress counteracts the pro-apoptotic process triggered by p53 up-regulation. More in general, the importance of eIF5A in the cellular stress response is illustrated by the finding that exposure to UV light promotes the binding of eIF5A to the ribosomes, whereas UV treatment complemented by the presence of GC7 inhibits such binding, allowing a decrease of de novo synthesis of p53 protein.
Keywords	colon cancer cell lines ; eIF5A ; GC7 ; p53 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Potassium Channel KCNH1 Activating Variants Cause Altered Functional and Morphological Ciliogenesis.

Napoli, Giulia / Panzironi, Noemi / Traversa, Alice / Catalanotto, Caterina / Pace, Valentina / Petrizzelli, Francesco / Giovannetti, Agnese / Lazzari, Sara / Cogoni, Carlo / Tartaglia, Marco / Carella, Massimo / Mazza, Tommaso / Pizzuti, Antonio / Parisi, Chiara / Caputo, Viviana

Molecular neurobiology

2022 Volume 59, Issue 8, Page(s) 4825–4838

Abstract: The primary cilium is a non-motile sensory organelle that extends from the surface of most vertebrate cells and transduces signals regulating proliferation, differentiation, and migration. Primary cilia dysfunctions have been observed in cancer and in a ... ...

Abstract	The primary cilium is a non-motile sensory organelle that extends from the surface of most vertebrate cells and transduces signals regulating proliferation, differentiation, and migration. Primary cilia dysfunctions have been observed in cancer and in a group of heterogeneous disorders called ciliopathies, characterized by renal and liver cysts, skeleton and limb abnormalities, retinal degeneration, intellectual disability, ataxia, and heart disease and, recently, in autism spectrum disorder, schizophrenia, and epilepsy. The potassium voltage-gated channel subfamily H member 1 (KCNH1) gene encodes a member of the EAG (ether-à-go-go) family, which controls potassium flux regulating resting membrane potential in both excitable and non-excitable cells and is involved in intracellular signaling, cell proliferation, and tumorigenesis. KCNH1 missense variants have been associated with syndromic neurodevelopmental disorders, including Zimmermann-Laband syndrome 1 (ZLS1, MIM #135500), Temple-Baraitser syndrome (TMBTS, MIM #611816), and, recently, with milder phenotypes as epilepsy. In this work, we provide evidence that KCNH1 localizes at the base of the cilium in pre-ciliary vesicles and ciliary pocket of human dermal fibroblasts and retinal pigment epithelial (hTERT RPE1) cells and that the pathogenic missense variants (L352V and R330Q; NP_002229.1) perturb cilia morphology, assembly/disassembly, and Sonic Hedgehog signaling, disclosing a multifaceted role of the protein. The study of KCNH1 localization, its functions related to primary cilia, and the alterations introduced by mutations in ciliogenesis, cell cycle coordination, cilium morphology, and cilia signaling pathways could help elucidate the molecular mechanisms underlying neurological phenotypes and neurodevelopmental disorders not considered as classical ciliopathies but for which a significant role of primary cilia is emerging.
MeSH term(s)	Abnormalities, Multiple ; Autism Spectrum Disorder ; Ciliopathies/genetics ; Ciliopathies/pathology ; Craniofacial Abnormalities ; Epilepsy/genetics ; Ether-A-Go-Go Potassium Channels/genetics ; Ether-A-Go-Go Potassium Channels/metabolism ; Fibromatosis, Gingival ; Hallux/abnormalities ; Hand Deformities, Congenital ; Hedgehog Proteins/metabolism ; Humans ; Intellectual Disability ; Nails, Malformed ; Potassium/metabolism ; Thumb/abnormalities
Chemical Substances	Ether-A-Go-Go Potassium Channels ; Hedgehog Proteins ; KCNH1 protein, human ; Potassium (RWP5GA015D)
Language	English
Publishing date	2022-05-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-022-02886-4
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Article ; Online: MicroRNA in Control of Gene Expression

Caterina Catalanotto / Carlo Cogoni / Giuseppe Zardo

International Journal of Molecular Sciences, Vol 17, Iss 10, p

An Overview of Nuclear Functions

2016 Volume 1712

Abstract	The finding that small non-coding RNAs (ncRNAs) are able to control gene expression in a sequence specific manner has had a massive impact on biology. Recent improvements in high throughput sequencing and computational prediction methods have allowed the discovery and classification of several types of ncRNAs. Based on their precursor structures, biogenesis pathways and modes of action, ncRNAs are classified as small interfering RNAs (siRNAs), microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), endogenous small interfering RNAs (endo-siRNAs or esiRNAs), promoter associate RNAs (pRNAs), small nucleolar RNAs (snoRNAs) and sno-derived RNAs. Among these, miRNAs appear as important cytoplasmic regulators of gene expression. miRNAs act as post-transcriptional regulators of their messenger RNA (mRNA) targets via mRNA degradation and/or translational repression. However, it is becoming evident that miRNAs also have specific nuclear functions. Among these, the most studied and debated activity is the miRNA-guided transcriptional control of gene expression. Although available data detail quite precisely the effectors of this activity, the mechanisms by which miRNAs identify their gene targets to control transcription are still a matter of debate. Here, we focus on nuclear functions of miRNAs and on alternative mechanisms of target recognition, at the promoter lavel, by miRNAs in carrying out transcriptional gene silencing.
Keywords	microRNA ; miRNA inducing silencing complex (miRISC) ; transcriptional control ; epigenetics ; nuclear function ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2016-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Modifications of H3K4 methylation levels are associated with DNA hypermethylation in acute myeloid leukemia.

Scalea, Stefania / Maresca, Carmen / Catalanotto, Caterina / Marino, Rachele / Cogoni, Carlo / Reale, Anna / Zampieri, Michele / Zardo, Giuseppe

The FEBS journal

2019 Volume 287, Issue 6, Page(s) 1155–1175

Abstract: The 'instructive model' of aberrant DNA methylation in human tumors is based on the observation that CpG islands prone to hypermethylation in cancers are embedded in chromatin enriched in H3K27me3 in human embryonic stem cells (hESC). Recent studies also ...

Abstract	The 'instructive model' of aberrant DNA methylation in human tumors is based on the observation that CpG islands prone to hypermethylation in cancers are embedded in chromatin enriched in H3K27me3 in human embryonic stem cells (hESC). Recent studies also link methylation of CpG islands to the methylation status of H3K4, where H3K4me3 is inversely correlated with DNA methylation. To provide insight into these conflicting findings, we generated DNA methylation profiles for acute myeloid leukemia samples from patients and leukemic cell lines and integrated them with publicly available ChIp-seq data, containing H3K4me3 and H3K27me3 CpG island occupation in hESC, or hematopoietic stem or progenitor cells (hHSC/MPP). Hypermethylated CpG islands in AML samples displayed H3K27me3 enrichments in hESC and hHSC/MPP; however, ChIp analysis of specific hypermethylated CpG islands revealed a significant reduction in H3K4me3 signal with a concomitant increase in H3K4me0 levels as opposed to a nonsignificant increase in H3K27me3 marks. The integration of AML DNA methylation profiles with the ChIp-seq data in hESC and hHSC/MPP also led to the identification of Iroquois homeobox 2 (IRX2) as a previously unknown factor promoting differentiation of leukemic cells. Our results indicate that in contrast to the 'instructive model', H3K4me3 levels are strongly associated with DNA methylation patterns in AML and have a role in the regulation of critical genes, such as the putative tumor suppressor IRX2.
MeSH term(s)	Cell Line, Tumor ; DNA Methylation/genetics ; Histones/metabolism ; Homeodomain Proteins/genetics ; Humans ; Leukemia, Myeloid, Acute/genetics ; Transcription Factors/genetics
Chemical Substances	Histones ; Homeodomain Proteins ; IRX2 protein, human ; Transcription Factors ; histone H3 trimethyl Lys4
Language	English
Publishing date	2019-10-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.15086
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Article: Modifications of H3K4 methylation levels are associated with DNA hypermethylation in acute myeloid leukemia

Scalea, Stefania / Maresca, Carmen / Catalanotto, Caterina / Marino, Rachele / Cogoni, Carlo / Reale, Anna / Zampieri, Michele / Zardo, Giuseppe

FEBS journal. 2020 Mar., v. 287, no. 6

2020

Abstract: The ‘instructive model’ of aberrant DNA methylation in human tumors is based on the observation that CpG islands prone to hypermethylation in cancers are embedded in chromatin enriched in H3K27me3 in human embryonic stem cells (hESC). Recent studies also ...

Abstract	The ‘instructive model’ of aberrant DNA methylation in human tumors is based on the observation that CpG islands prone to hypermethylation in cancers are embedded in chromatin enriched in H3K27me3 in human embryonic stem cells (hESC). Recent studies also link methylation of CpG islands to the methylation status of H3K4, where H3K4me3 is inversely correlated with DNA methylation. To provide insight into these conflicting findings, we generated DNA methylation profiles for acute myeloid leukemia samples from patients and leukemic cell lines and integrated them with publicly available ChIp‐seq data, containing H3K4me3 and H3K27me3 CpG island occupation in hESC, or hematopoietic stem or progenitor cells (hHSC/MPP). Hypermethylated CpG islands in AML samples displayed H3K27me3 enrichments in hESC and hHSC/MPP; however, ChIp analysis of specific hypermethylated CpG islands revealed a significant reduction in H3K4me3 signal with a concomitant increase in H3K4me0 levels as opposed to a nonsignificant increase in H3K27me3 marks. The integration of AML DNA methylation profiles with the ChIp‐seq data in hESC and hHSC/MPP also led to the identification of Iroquois homeobox 2 (IRX2) as a previously unknown factor promoting differentiation of leukemic cells. Our results indicate that in contrast to the ‘instructive model’, H3K4me3 levels are strongly associated with DNA methylation patterns in AML and have a role in the regulation of critical genes, such as the putative tumor suppressor IRX2.
Keywords	DNA hypermethylation ; chromatin ; chromatin immunoprecipitation ; genomic islands ; humans ; myeloid leukemia ; occupations
Language	English
Dates of publication	2020-03
Size	p. 1155-1175.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	NAL-AP-2-clean ; JOURNAL ARTICLE
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.15086
Database	NAL-Catalogue (AGRICOLA)

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