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Article ; Online: Noncoding RNAs and RNA-binding proteins: emerging governors of liver physiology and metabolic diseases.

Sommerauer, Christian / Kutter, Claudia

American journal of physiology. Cell physiology

2022 Volume 323, Issue 4, Page(s) C1003–C1017

Abstract: The liver holds central roles in detoxification, energy metabolism, and whole body homeostasis but can develop malignant phenotypes when being chronically overwhelmed with fatty acids and glucose. The global rise of metabolic dysfunction-associated fatty ...

Abstract	The liver holds central roles in detoxification, energy metabolism, and whole body homeostasis but can develop malignant phenotypes when being chronically overwhelmed with fatty acids and glucose. The global rise of metabolic dysfunction-associated fatty liver disease (MAFLD) is already affecting a quarter of the global population. Pharmaceutical treatment options against different stages of MAFLD do not yet exist, and several clinical trials against hepatic transcription factors and other proteins have failed. However, emerging roles of noncoding RNAs, including long (lncRNA) and short noncoding RNAs (sRNA), in various cellular processes pose exciting new avenues for treatment interventions. Actions of noncoding RNAs mostly rely on interactions with proteins, whereby the noncoding RNA fine-tunes protein function in a process termed riboregulation. The developmental stage-, disease stage-, and cell type-specific nature of noncoding RNAs harbors enormous potential to precisely target certain cellular pathways in a spatiotemporally defined manner. Proteins interacting with RNAs can be categorized into canonical or noncanonical RNA-binding proteins (RBPs) depending on the existence of classical RNA-binding domains. Both, RNA- and RBP-centric methods have generated new knowledge of the RNA-RBP interface and added an additional regulatory layer. In this review, we summarize recent advances in how RBP-lncRNA interactions and various sRNAs shape cellular physiology and the development of liver diseases such as MAFLD and hepatocellular carcinoma.
MeSH term(s)	Fatty Acids ; Glucose ; Humans ; Liver Neoplasms ; Metabolic Diseases ; Pharmaceutical Preparations ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; RNA, Small Untranslated ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Transcription Factors/metabolism
Chemical Substances	Fatty Acids ; Pharmaceutical Preparations ; RNA, Long Noncoding ; RNA, Small Untranslated ; RNA-Binding Proteins ; Transcription Factors ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-08-15
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00232.2022
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Article ; Online: Expression Profiles of Estrogen-Regulated MicroRNAs in Cancer Cells.

Archer, Amena / Kutter, Claudia / Williams, Cecilia

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2418, Page(s) 313–343

Abstract: MicroRNAs play critical roles through their impact on posttranscriptional gene regulation. In cancer, they can act as oncogenes or tumor suppressors and can also function as biomarkers. Here, we describe a method for robust characterization of estrogen- ... ...

Abstract	MicroRNAs play critical roles through their impact on posttranscriptional gene regulation. In cancer, they can act as oncogenes or tumor suppressors and can also function as biomarkers. Here, we describe a method for robust characterization of estrogen-regulated microRNA profiles. The activity of estrogen is mediated by two nuclear receptors, estrogen receptor alpha and estrogen receptor beta, and a transmembrane G-protein coupled estrogen receptor 1. This chapter details how to prepare cells for optimal estrogen response, directions for estrogen treatment, RNA extraction, different microRNA profiling approaches, and subsequent confirmations.
MeSH term(s)	Breast Neoplasms/genetics ; Estrogen Receptor alpha/genetics ; Estrogen Receptor alpha/metabolism ; Estrogen Receptor beta/genetics ; Estrogens/pharmacology ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism
Chemical Substances	Estrogen Receptor alpha ; Estrogen Receptor beta ; Estrogens ; MicroRNAs
Language	English
Publishing date	2022-02-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1920-9_18
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Book ; Thesis: Auswirkungen der peroralen Intubation auf die Kiefergelenksfunktionen unter dem Einfluß verschiedener Muskelrelaxantien und pathologischer Kiefergelenksvorbefunde und Geschlecht

Kutter, Claudia

1992

Author's details	vorgelegt von Claudia Kutter
Size	1 Mikrofiche : 24x
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Mainz, Univ., Diss., 1992
Note	Mikroreprod. eines Ms. 77, [5] Bl.: graph. Darst.
HBZ-ID	HT004383516
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Article ; Online: Genome Size Reduction and Transposon Activity Impact tRNA Gene Diversity While Ensuring Translational Stability in Birds.

Ottenburghs, Jente / Geng, Keyi / Suh, Alexander / Kutter, Claudia

Genome biology and evolution

2021 Volume 13, Issue 4

Abstract: As a highly diverse vertebrate class, bird species have adapted to various ecological systems. How this phenotypic diversity can be explained genetically is intensively debated and is likely grounded in differences in the genome content. Larger and more ... ...

Abstract	As a highly diverse vertebrate class, bird species have adapted to various ecological systems. How this phenotypic diversity can be explained genetically is intensively debated and is likely grounded in differences in the genome content. Larger and more complex genomes could allow for greater genetic regulation that results in more phenotypic variety. Surprisingly, avian genomes are much smaller compared to other vertebrates but contain as many protein-coding genes as other vertebrates. This supports the notion that the phenotypic diversity is largely determined by selection on non-coding gene sequences. Transfer RNAs (tRNAs) represent a group of non-coding genes. However, the characteristics of tRNA genes across bird genomes have remained largely unexplored. Here, we exhaustively investigated the evolution and functional consequences of these crucial translational regulators within bird species and across vertebrates. Our dense sampling of 55 avian genomes representing each bird order revealed an average of 169 tRNA genes with at least 31% being actively used. Unlike other vertebrates, avian tRNA genes are reduced in number and complexity but are still in line with vertebrate wobble pairing strategies and mutation-driven codon usage. Our detailed phylogenetic analyses further uncovered that new tRNA genes can emerge through multiplication by transposable elements. Together, this study provides the first comprehensive avian and cross-vertebrate tRNA gene analyses and demonstrates that tRNA gene evolution is flexible albeit constrained within functional boundaries of general mechanisms in protein translation.
MeSH term(s)	Animals ; Birds/genetics ; Birds/metabolism ; Codon Usage ; Evolution, Molecular ; Genome ; Genome Size ; Mutation ; Protein Biosynthesis ; RNA, Transfer/chemistry ; RNA, Transfer/genetics ; RNA, Transfer/metabolism ; Short Interspersed Nucleotide Elements ; Synteny
Chemical Substances	RNA, Transfer (9014-25-9)
Language	English
Publishing date	2021-02-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2495328-3
ISSN	1759-6653 ; 1759-6653
ISSN (online)	1759-6653
ISSN	1759-6653
DOI	10.1093/gbe/evab016
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Article ; Online: Cell type-specific analysis by single-cell profiling identifies a stable mammalian tRNA-mRNA interface and increased translation efficiency in neurons.

Gao, William / Gallardo-Dodd, Carlos J / Kutter, Claudia

Genome research

2021 Volume 32, Issue 1, Page(s) 97–110

Abstract: The correlation between codon and anticodon pools influences the efficiency of translation, but whether differences exist in these pools across individual cells is unknown. We determined that codon usage and amino acid demand are highly stable across ... ...

Abstract	The correlation between codon and anticodon pools influences the efficiency of translation, but whether differences exist in these pools across individual cells is unknown. We determined that codon usage and amino acid demand are highly stable across different cell types using available mouse and human single-cell RNA-sequencing atlases. After showing the robustness of ATAC-sequencing measurements for the analysis of tRNA gene usage, we quantified anticodon usage and amino acid supply in both mouse and human single-cell ATAC-seq atlases. We found that tRNA gene usage is overall coordinated across cell types, except in neurons, which clustered separately from other cell types. Integration of these data sets revealed a strong and statistically significant correlation between amino acid supply and demand across almost all cell types. Neurons have an enhanced translation efficiency over other cell types, driven by an increased supply of tRNA
MeSH term(s)	Animals ; Anticodon/genetics ; Codon ; Mice ; Neurons/metabolism ; Protein Biosynthesis ; RNA, Messenger/genetics ; RNA, Transfer/genetics ; RNA, Transfer/metabolism
Chemical Substances	Anticodon ; Codon ; RNA, Messenger ; RNA, Transfer (9014-25-9)
Language	English
Publishing date	2021-12-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.275944.121
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Article ; Online: Intrinsic deletion at 10q23.31, including the

Geng, Keyi / Merino, Lara G / Veiga, Raül G / Sommerauer, Christian / Epperlein, Janine / Brinkman, Eva K / Kutter, Claudia

Life science alliance

2023 Volume 7, Issue 2

Abstract: The CRISPR-Cas9 system is a powerful tool for studying gene functions and holds potential for disease treatment. However, precise genome editing requires thorough assessments to minimize unintended on- and off-target effects. Here, we report an ... ...

Abstract	The CRISPR-Cas9 system is a powerful tool for studying gene functions and holds potential for disease treatment. However, precise genome editing requires thorough assessments to minimize unintended on- and off-target effects. Here, we report an unexpected 283-kb deletion on Chromosome 10 (10q23.31) in chronic myelogenous leukemia-derived HAP1 cells, which are frequently used in CRISPR screens. The deleted region encodes regulatory genes, including
MeSH term(s)	Humans ; CRISPR-Cas Systems/genetics ; Gene Editing ; Genome ; Chromosome Structures ; Phenotype ; Neoplasms/genetics ; PTEN Phosphohydrolase/genetics
Chemical Substances	PTEN protein, human (EC 3.1.3.67) ; PTEN Phosphohydrolase (EC 3.1.3.67)
Language	English
Publishing date	2023-11-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202302128
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Article ; Online: Inhibition of Respiratory Syncytial Virus Infection by Small Non-Coding RNA Fragments.

Pålsson, Sandra Axberg / Sekar, Vaishnovi / Kutter, Claudia / Friedländer, Marc R / Spetz, Anna-Lena

International journal of molecular sciences

2022 Volume 23, Issue 11

Abstract: Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants, immunocompromised individuals and the elderly. As the only current specific treatment options for RSV are monoclonal antibodies, there is a need for efficacious ... ...

Abstract	Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants, immunocompromised individuals and the elderly. As the only current specific treatment options for RSV are monoclonal antibodies, there is a need for efficacious antiviral treatments against RSV to be developed. We have previously shown that a group of synthetic non-coding single-stranded DNA oligonucleotides with lengths of 25-40 nucleotides can inhibit RSV infection in vitro and in vivo. Based on this, herein, we investigate whether naturally occurring single-stranded small non-coding RNA (sncRNA) fragments present in the airways have antiviral effects against RSV infection. From publicly available sequencing data, we selected sncRNA fragments such as YRNAs, tRNAs and rRNAs present in human bronchoalveolar lavage fluid (BALF) from healthy individuals. We utilized a GFP-expressing RSV to show that pre-treatment with the selected sncRNA fragments inhibited RSV infection in A549 cells in vitro. Furthermore, by using a flow cytometry-based binding assay, we demonstrate that these naturally occurring sncRNAs fragments inhibit viral infection most likely by binding to the RSV entry receptor nucleolin and thereby preventing the virus from binding to host cells, either directly or via steric hindrance. This finding highlights a new function of sncRNAs and displays the possibility of using naturally occurring sncRNAs as treatments against RSV.
MeSH term(s)	A549 Cells ; Aged ; Antiviral Agents/pharmacology ; Humans ; Infant ; RNA, Small Untranslated/genetics ; Respiratory Syncytial Virus Infections/prevention & control ; Respiratory Syncytial Virus, Human/genetics
Chemical Substances	Antiviral Agents ; RNA, Small Untranslated
Language	English
Publishing date	2022-05-26
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/ijms23115990
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Article ; Online: 5´XP sRNA-seq: efficient identification of transcripts with and without 5´ phosphorylation reveals evolutionary conserved small RNA.

Kugelberg, Unn / Nätt, Daniel / Skog, Signe / Kutter, Claudia / Öst, Anita

RNA biology

2020 Volume 18, Issue 11, Page(s) 1588–1599

Abstract: Small RNA (sRNA) sequencing has been critical for our understanding of many cellular processes, including gene regulation. Nonetheless, the varying biochemical properties of sRNA, such as 5´ nucleotide modifications, make many sRNA subspecies ... ...

Abstract	Small RNA (sRNA) sequencing has been critical for our understanding of many cellular processes, including gene regulation. Nonetheless, the varying biochemical properties of sRNA, such as 5´ nucleotide modifications, make many sRNA subspecies incompatible with common protocols for sRNA sequencing. Here we describe 5XP-seq that outlines a novel strategy that captures a more complete picture of sRNA. By tagging 5´P sRNA during library preparation, 5XP-seq combines an open approach that includes all types of 5'-terminal modifications (5´X), with a selective approach for 5-phosphorylated sRNA (5´P). We show that 5XP-seq not only enriches phosphorylated miRNA and piRNA but successfully discriminates these sRNA from all other sRNA species. We further demonstrate the importance of this strategy by successful inter-species validation of sRNAs that would have otherwise failed, including human to insect translation of several tRNA (tRFs) and rRNA (rRFs) fragments. By combining 5´ insensitive library strategies with 5´ sensitive tagging, we have successfully tackled an intrinsic bias in modern sRNA sequencing that will help us reveal the true complexity and the evolutionary significance of the sRNA world.
MeSH term(s)	Animals ; Drosophila Proteins ; Drosophila melanogaster/genetics ; Drosophila melanogaster/growth & development ; Drosophila melanogaster/metabolism ; Embryo, Nonmammalian/cytology ; Embryo, Nonmammalian/metabolism ; Evolution, Molecular ; Gene Library ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Phosphorylation ; RNA, Ribosomal/genetics ; RNA, Ribosomal/metabolism ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; RNA, Small Untranslated/genetics ; RNA, Small Untranslated/metabolism ; RNA-Seq/methods
Chemical Substances	Drosophila Proteins ; MicroRNAs ; RNA, Ribosomal ; RNA, Small Interfering ; RNA, Small Untranslated
Language	English
Publishing date	2020-12-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2159587-2
ISSN	1555-8584 ; 1555-8584
ISSN (online)	1555-8584
ISSN	1555-8584
DOI	10.1080/15476286.2020.1861770
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Article ; Online: Estrogen receptor activation remodels TEAD1 gene expression to alleviate hepatic steatosis.

Molecular systems biology

2024 Volume 20, Issue 4, Page(s) 374–402

Abstract: Sex-based differences in obesity-related hepatic malignancies suggest the protective roles of estrogen. Using a preclinical model, we dissected estrogen receptor (ER) isoform-driven molecular responses in high-fat diet (HFD)-induced liver diseases of ... ...

Abstract	Sex-based differences in obesity-related hepatic malignancies suggest the protective roles of estrogen. Using a preclinical model, we dissected estrogen receptor (ER) isoform-driven molecular responses in high-fat diet (HFD)-induced liver diseases of male and female mice treated with or without an estrogen agonist by integrating liver multi-omics data. We found that selective ER activation recovers HFD-induced molecular and physiological liver phenotypes. HFD and systemic ER activation altered core liver pathways, beyond lipid metabolism, that are consistent between mice and primates. By including patient cohort data, we uncovered that ER-regulated enhancers govern central regulatory and metabolic genes with clinical significance in metabolic dysfunction-associated steatotic liver disease (MASLD) patients, including the transcription factor TEAD1. TEAD1 expression increased in MASLD patients, and its downregulation by short interfering RNA reduced intracellular lipid content. Subsequent TEAD small molecule inhibition improved steatosis in primary human hepatocyte spheroids by suppressing lipogenic pathways. Thus, TEAD1 emerged as a new therapeutic candidate whose inhibition ameliorates hepatic steatosis.
MeSH term(s)	Animals ; Female ; Humans ; Male ; Mice ; Diet, High-Fat/adverse effects ; Estrogens ; Fatty Liver/genetics ; Fatty Liver/metabolism ; Gene Expression ; Liver/metabolism ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/genetics ; Non-alcoholic Fatty Liver Disease/metabolism ; Receptors, Estrogen/genetics ; Receptors, Estrogen/metabolism ; Receptors, Estrogen/therapeutic use ; TEA Domain Transcription Factors
Chemical Substances	Estrogens ; Receptors, Estrogen ; TEA Domain Transcription Factors ; TEAD1 protein, human ; Tead1 protein, mouse
Language	English
Publishing date	2024-03-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2193510-5
ISSN	1744-4292 ; 1744-4292
ISSN (online)	1744-4292
ISSN	1744-4292
DOI	10.1038/s44320-024-00024-x
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Article ; Online: Inhibition of Respiratory Syncytial Virus Infection by Small Non-Coding RNA Fragments

Sandra Axberg Pålsson / Vaishnovi Sekar / Claudia Kutter / Marc R. Friedländer / Anna-Lena Spetz

International Journal of Molecular Sciences, Vol 23, Iss 5990, p

2022 Volume 5990

Abstract	Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants, immunocompromised individuals and the elderly. As the only current specific treatment options for RSV are monoclonal antibodies, there is a need for efficacious antiviral treatments against RSV to be developed. We have previously shown that a group of synthetic non-coding single-stranded DNA oligonucleotides with lengths of 25–40 nucleotides can inhibit RSV infection in vitro and in vivo. Based on this, herein, we investigate whether naturally occurring single-stranded small non-coding RNA (sncRNA) fragments present in the airways have antiviral effects against RSV infection. From publicly available sequencing data, we selected sncRNA fragments such as YRNAs, tRNAs and rRNAs present in human bronchoalveolar lavage fluid (BALF) from healthy individuals. We utilized a GFP-expressing RSV to show that pre-treatment with the selected sncRNA fragments inhibited RSV infection in A549 cells in vitro. Furthermore, by using a flow cytometry-based binding assay, we demonstrate that these naturally occurring sncRNAs fragments inhibit viral infection most likely by binding to the RSV entry receptor nucleolin and thereby preventing the virus from binding to host cells, either directly or via steric hindrance. This finding highlights a new function of sncRNAs and displays the possibility of using naturally occurring sncRNAs as treatments against RSV.
Keywords	Respiratory Syncytial Virus (RSV) ; sncRNAs ; tRNA ; YRNA ; rRNA ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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