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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 ; 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: 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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Article: Unifying homology effects.

Cogoni, Carlo

Nature genetics

2002 Volume 30, Issue 3, Page(s) 245–246

MeSH term(s)	Animals ; Drosophila ; Gene Silencing ; Genes, Fungal ; Neurospora crassa/cytology ; Neurospora crassa/genetics ; Sequence Homology, Nucleic Acid
Language	English
Publishing date	2002-03
Publishing country	United States
Document type	News
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/ng0302-245
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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: Quelling targets the rDNA locus and functions in rDNA copy number control

Cecere Germano / Cogoni Carlo

BMC Microbiology, Vol 9, Iss 1, p

2009 Volume 44

Abstract: Abstract Background RNA silencing occurs in a broad range of organisms. Although its ancestral function is probably related to the genome defense mechanism against repetitive selfish elements, it has been found that RNA silencing regulates different ... ...

Abstract	Abstract Background RNA silencing occurs in a broad range of organisms. Although its ancestral function is probably related to the genome defense mechanism against repetitive selfish elements, it has been found that RNA silencing regulates different cellular processes such as gene expression and chromosomal segregation. In Neurospora crassa , a RNA silencing mechanism, called quelling, acts to repress the expression of transgenes and transposons, but until now no other cellular functions have been shown to be regulated by this mechanism. Results Here, we detected by northern blotting endogenous short interfering RNA (siRNAs) from the repetitive ribosomal DNA locus (rDNA) that are loaded onto the argonaute protein QDE-2. Moreover, we found a bidirectional transcription that can generate double strand RNA (dsRNA) molecules. Interestingly, quelling mutants have a reduced rDNA gene copy number. Conclusion Our finding could suggest a new biological function for RNA silencing in the maintenance of the integrity and stability of the Neurospora rDNA locus.
Keywords	Microbiology ; QR1-502 ; Science ; Q ; DOAJ:Microbiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
Subject code	612
Language	English
Publishing date	2009-02-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: MicroRNA landscape in Alzheimer's disease.

Cogoni, Carlo / Ruberti, Francesca / Barbato, Christian

CNS & neurological disorders drug targets

2014 Volume 14, Issue 2, Page(s) 168–175

Abstract: Individual microRNAs and/or microRNA signatures were associated with Alzheimer's disease (AD). We report here the recent advances brought to the identification of microRNA changes in AD brain and their biological function in the molecular pathways ... ...

Abstract	Individual microRNAs and/or microRNA signatures were associated with Alzheimer's disease (AD). We report here the recent advances brought to the identification of microRNA changes in AD brain and their biological function in the molecular pathways associated with the disease. This field represents a fertile route to understand the pathogenic mechanisms underlying Alzheimer's disease. In addition we review recent studies aimed to discover promising biomarkers for AD diagnosis by microRNA expression profiles of biofluids from AD patients.
MeSH term(s)	Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Brain/metabolism ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism
Chemical Substances	MicroRNAs
Language	English
Publishing date	2014-10-17
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2228394-8
ISSN	1996-3181 ; 1871-5273
ISSN (online)	1996-3181
ISSN	1871-5273
DOI	10.2174/1871527314666150116123305
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Article ; Online: From transcription to translation

Giorgi Corinna / Cogoni Carlo / Catalanotto Caterina

Biomolecular Concepts, Vol 3, Iss 6, Pp 545-

new insights in the structure and function of Argonaute protein

2012 Volume 559

Abstract: Argonaute proteins play a central role in gene silencing pathways mediated by small RNA molecules. The ancestral function of small RNA-dependent silencing is related to genome protection against parasitic nucleic acids, such as transposons and viruses. ... ...

Abstract	Argonaute proteins play a central role in gene silencing pathways mediated by small RNA molecules. The ancestral function of small RNA-dependent silencing is related to genome protection against parasitic nucleic acids, such as transposons and viruses. However, new classes of small RNAs are continuously being uncovered in all higher eukaryotes in which they play important functions in processes ranging from embryonic development to differentiation to cell proliferation and metabolism. Small RNAs have variegated biogenesis pathways and accomplish distinct functions. Nevertheless, it appears that all small RNAs work merely as guides in recognizing the target RNAs invariably relying on the interaction with Argonaute proteins and associated factors for their biological function. Here, we discuss recent findings on the structure and regulation of mammalian Argonaute proteins and overview the various roles that these versatile proteins play in regulating gene expression.
Keywords	argonaute ; gene expression ; gw182 ; mirna ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2012-12-01T00:00:00Z
Publisher	De Gruyter
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Quelling targets the rDNA locus and functions in rDNA copy number control.

Cecere, Germano / Cogoni, Carlo

BMC microbiology

2009 Volume 9, Page(s) 44

Abstract: Background: RNA silencing occurs in a broad range of organisms. Although its ancestral function is probably related to the genome defense mechanism against repetitive selfish elements, it has been found that RNA silencing regulates different cellular ... ...

Abstract	Background: RNA silencing occurs in a broad range of organisms. Although its ancestral function is probably related to the genome defense mechanism against repetitive selfish elements, it has been found that RNA silencing regulates different cellular processes such as gene expression and chromosomal segregation. In Neurospora crassa, a RNA silencing mechanism, called quelling, acts to repress the expression of transgenes and transposons, but until now no other cellular functions have been shown to be regulated by this mechanism. Results: Here, we detected by northern blotting endogenous short interfering RNA (siRNAs) from the repetitive ribosomal DNA locus (rDNA) that are loaded onto the argonaute protein QDE-2. Moreover, we found a bidirectional transcription that can generate double strand RNA (dsRNA) molecules. Interestingly, quelling mutants have a reduced rDNA gene copy number. Conclusion: Our finding could suggest a new biological function for RNA silencing in the maintenance of the integrity and stability of the Neurospora rDNA locus.
MeSH term(s)	Blotting, Northern ; DNA, Ribosomal/metabolism ; Fungal Proteins/metabolism ; Gene Dosage ; Neurospora crassa/genetics ; Neurospora crassa/physiology ; RNA Interference ; RNA, Small Interfering/metabolism
Chemical Substances	DNA, Ribosomal ; Fungal Proteins ; QDE-2 protein, Neurospora crassa ; RNA, Small Interfering
Language	English
Publishing date	2009-02-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1471-2180
ISSN (online)	1471-2180
DOI	10.1186/1471-2180-9-44
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