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Article ; Online: The End of Carnivalism, or The Making of the Corpus Lucianeum

Markus Hafner

Araucaria, Vol 21, Iss 41, Pp 209-

2019 Volume 231

Abstract: En un pasaje clave para entender la obra de Luciano, Piscator 25–27, el filósofo Diógenes de Sinope se queja de que Parresíades, una figura de autoría parecida a Luciano, no se burla de los filósofos dentro de los límites carnavalescos del festival, como ...

Abstract	En un pasaje clave para entender la obra de Luciano, Piscator 25–27, el filósofo Diógenes de Sinope se queja de que Parresíades, una figura de autoría parecida a Luciano, no se burla de los filósofos dentro de los límites carnavalescos del festival, como lo hacía la Comedia Vieja, a la que tanto debe la obra de Luciano, sino mediante constantes publicaciones de escritos. Esta afirmación adquiere aún mayor importancia por el hecho de que el Piscator pertenece a un grupo de textos que muestra evidentes referencias cruzadas a otros escritos del corpus (como Pro imaginibus, Apologia o Fugitivi). Al crear indirectamente comentarios de autoría y referencias intertextuales a través de su obra ‘multitemática’ – por así decir, una (auto)bibliobiografía escondida –, Luciano refuerza la idea de una obra literaria orgánica y un corpus coherente que se encuentra – a pesar de la variatio temática – bien divulgado y lejos de la excepcionalidad carnavalesca. Así, la estética de la trasgresión perpetua está relacionada de manera única con la construcción de la auto-referencialidad como autor en las sátiras de Luciano.
Keywords	carnavalismo ; publicación ; intratextualidad ; biobibliografía ; pseudo ; lucianea ; ficciones autoriales ; History of scholarship and learning. The humanities ; AZ20-999 ; Political science ; J ; Philosophy (General) ; B1-5802
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Universidad de Sevilla
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Multiple capsid protein binding sites mediate selective packaging of the alphavirus genomic RNA

Rebecca S. Brown / Dimitrios G. Anastasakis / Markus Hafner / Margaret Kielian

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 16

Abstract: Alphaviruses need to selectively package genomic viral RNA for transmission, but the packaging mechanism remains unclear. Here, Brown et al. combine PAR-CLIP with biotinylated capsid protein (Cp) retrieval and identify multiple Cp binding sites on ... ...

Abstract	Alphaviruses need to selectively package genomic viral RNA for transmission, but the packaging mechanism remains unclear. Here, Brown et al. combine PAR-CLIP with biotinylated capsid protein (Cp) retrieval and identify multiple Cp binding sites on genomic viral RNA that promote virion formation.
Keywords	Science ; Q
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Chemoproteomic capture of RNA binding activity in living cells

Andrew J. Heindel / Jeffrey W. Brulet / Xiantao Wang / Michael W. Founds / Adam H. Libby / Dina L. Bai / Michael C. Lemke / David M. Leace / Thurl E. Harris / Markus Hafner / Ku-Lung Hsu

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 14

Abstract: Abstract Proteomic methods for RNA interactome capture (RIC) rely principally on crosslinking native or labeled cellular RNA to enrich and investigate RNA-binding protein (RBP) composition and function in cells. The ability to measure RBP activity at ... ...

Abstract	Abstract Proteomic methods for RNA interactome capture (RIC) rely principally on crosslinking native or labeled cellular RNA to enrich and investigate RNA-binding protein (RBP) composition and function in cells. The ability to measure RBP activity at individual binding sites by RIC, however, has been more challenging due to the heterogenous nature of peptide adducts derived from the RNA-protein crosslinked site. Here, we present an orthogonal strategy that utilizes clickable electrophilic purines to directly quantify protein-RNA interactions on proteins through photoaffinity competition with 4-thiouridine (4SU)-labeled RNA in cells. Our photo-activatable-competition and chemoproteomic enrichment (PACCE) method facilitated detection of >5500 cysteine sites across ~3000 proteins displaying RNA-sensitive alterations in probe binding. Importantly, PACCE enabled functional profiling of canonical RNA-binding domains as well as discovery of moonlighting RNA binding activity in the human proteome. Collectively, we present a chemoproteomic platform for global quantification of protein-RNA binding activity in living cells.
Keywords	Science ; Q
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Matrin3 regulates mitotic spindle dynamics by controlling alternative splicing of CDC14B

Bruna R. Muys / Roshan L. Shrestha / Dimitrios G. Anastasakis / Lorinc Pongor / Xiao Ling Li / Ioannis Grammatikakis / Ahsan Polash / Raj Chari / Myriam Gorospe / Curtis C. Harris / Mirit I. Aladjem / Munira A. Basrai / Markus Hafner / Ashish Lal

Cell Reports, Vol 42, Iss 3, Pp 112260- (2023)

2023

Abstract: Summary: Matrin3 is an RNA-binding protein that regulates diverse RNA-related processes, including mRNA splicing. Although Matrin3 has been intensively studied in neurodegenerative diseases, its function in cancer remains unclear. Here, we report Matrin3- ...

Abstract	Summary: Matrin3 is an RNA-binding protein that regulates diverse RNA-related processes, including mRNA splicing. Although Matrin3 has been intensively studied in neurodegenerative diseases, its function in cancer remains unclear. Here, we report Matrin3-mediated regulation of mitotic spindle dynamics in colorectal cancer (CRC) cells. We comprehensively identified RNAs bound and regulated by Matrin3 in CRC cells and focused on CDC14B, one of the top Matrin3 targets. Matrin3 knockdown results in increased inclusion of an exon containing a premature termination codon in the CDC14B transcript and simultaneous down-regulation of the standard CDC14B transcript. Knockdown of CDC14B phenocopies the defects in mitotic spindle dynamics upon Matrin3 knockdown, and the elongated and misoriented mitotic spindle observed upon Matrin3 knockdown are rescued upon overexpression of CDC14B, suggesting that CDC14B is a key downstream effector of Matrin3. Collectively, these data reveal a role for the Matrin3/CDC14B axis in control of mitotic spindle dynamics.
Keywords	CP: Cell biology ; CP: Molecular biology ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: MicroRNA 3928 Suppresses Glioblastoma through Downregulation of Several Oncogenes and Upregulation of p53

Elizabeth Q. X. Mulcahy / Ying Zhang / Rossymar R. Colόn / Shelby R. Cain / Myron K. Gibert / Collin J. Dube / Markus Hafner / Roger Abounader

International Journal of Molecular Sciences, Vol 23, Iss 3930, p

2022 Volume 3930

Abstract: Glioblastoma (GBM) is the most frequent and lethal primary malignant brain tumor. Despite decades of research, therapeutic advances that significantly prolong life are non-existent. In recent years, microRNAs (miRNAs) have been a focus of study in the ... ...

Abstract	Glioblastoma (GBM) is the most frequent and lethal primary malignant brain tumor. Despite decades of research, therapeutic advances that significantly prolong life are non-existent. In recent years, microRNAs (miRNAs) have been a focus of study in the pathobiology of cancer because of their ability to simultaneously regulate multiple genes. The aim of this study was to determine the functional and mechanistic effects of miR-3928 in GBM both in vitro and in vivo. To the best of our knowledge, this is the first article investigating the role of miR-3928 in GBM. We measured endogenous miR-3928 expression levels in a panel of patient-derived GBM tissue samples and cell lines. We found that GBM tissue samples and cell lines express lower levels of miR-3928 than normal brain cortex and astrocytes, respectively. Therefore, we hypothesized that miR-3928 is a tumor suppressive microRNA. We verified this hypothesis by showing that exogenous expression of miR-3928 has a strong inhibitory effect on both cell growth and invasiveness of GBM cells. Stable ex vivo overexpression of miR-3928 in GBM cells led to a reduction in tumor size in nude mice xenografts. We identified many targets (MDM2, CD44, DDX3X, HMGA2, CCND1, BRAF, ATOH8, and BMI1) of miR-3928. Interestingly, inhibition of the oncogene MDM2 also led to an upregulation of wild-type p53 expression and phosphorylation. In conclusion, we find that miR-3928, through the downregulation of several oncogenes and upregulation and activation of wild-type p53, is a strong tumor suppressor in GBM. Furthermore, the fact that miR-3928 can target many important dysregulated proteins in GBM suggests it might be a “master” regulatory microRNA that could be therapeutically exploited.
Keywords	miR-3928 ; glioblastoma ; p53 ; MDM2 ; CD44 ; DDX3X ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	500
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A miR-375/YAP axis regulates neuroendocrine differentiation and tumorigenesis in lung carcinoid cells

Xiaojing Yang / Jina Nanayakkara / Duncan Claypool / Sadegh Saghafinia / Justin J. M. Wong / Minqi Xu / Xiantao Wang / Christopher J. B. Nicol / Iacovos P. Michael / Markus Hafner / Xiaolong Yang / Neil Renwick

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 13

Abstract: Abstract Lung carcinoids are variably aggressive and mechanistically understudied neuroendocrine neoplasms (NENs). Here, we identified and elucidated the function of a miR-375/yes-associated protein (YAP) axis in lung carcinoid (H727) cells. miR-375 and ... ...

Abstract	Abstract Lung carcinoids are variably aggressive and mechanistically understudied neuroendocrine neoplasms (NENs). Here, we identified and elucidated the function of a miR-375/yes-associated protein (YAP) axis in lung carcinoid (H727) cells. miR-375 and YAP are respectively high and low expressed in wild-type H727 cells. Following lentiviral CRISPR/Cas9-mediated miR-375 depletion, we identified distinct transcriptomic changes including dramatic YAP upregulation. We also observed a significant decrease in neuroendocrine differentiation and substantial reductions in cell proliferation, transformation, and tumor growth in cell culture and xenograft mouse disease models. Similarly, YAP overexpression resulted in distinct and partially overlapping transcriptomic changes, phenocopying the effects of miR-375 depletion in the same models as above. Transient YAP knockdown in miR-375-depleted cells reversed the effects of miR-375 on neuroendocrine differentiation and cell proliferation. Pathways analysis and confirmatory real-time PCR studies of shared dysregulated target genes indicate that this axis controls neuroendocrine related functions such as neural differentiation, exocytosis, and secretion. Taken together, we provide compelling evidence that a miR-375/YAP axis is a critical mediator of neuroendocrine differentiation and tumorigenesis in lung carcinoid cells.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Characterizing Expression and Processing of Precursor and Mature Human tRNAs by Hydro-tRNAseq and PAR-CLIP

Tasos Gogakos / Miguel Brown / Aitor Garzia / Cindy Meyer / Markus Hafner / Thomas Tuschl

Cell Reports, Vol 20, Iss 6, Pp 1463-

2017 Volume 1475

Abstract: The participation of tRNAs in fundamental aspects of biology and disease necessitates an accurate, experimentally confirmed annotation of tRNA genes and curation of tRNA sequences. This has been challenging because RNA secondary structure, nucleotide ... ...

Abstract	The participation of tRNAs in fundamental aspects of biology and disease necessitates an accurate, experimentally confirmed annotation of tRNA genes and curation of tRNA sequences. This has been challenging because RNA secondary structure, nucleotide modifications, and tRNA gene multiplicity complicate sequencing and mapping efforts. To address these issues, we developed hydro-tRNAseq, a method based on partial alkaline RNA hydrolysis that generates fragments amenable for sequencing. To identify transcribed tRNA genes, we further complemented this approach with photoactivatable crosslinking and immunoprecipitation (PAR-CLIP) of SSB/La, a conserved protein involved in pre-tRNA processing. Our results show that approximately half of all predicted tRNA genes are transcribed in human cells. We also report nucleotide modification sites and their order of introduction, and we identify tRNA leaders, trailers, and introns. By using complementary sequencing-based methodologies, we present a human tRNA atlas and determine expression levels of mature and processing intermediates of tRNAs in human cells.
Keywords	Biology (General) ; QH301-705.5
Subject code	420
Language	English
Publishing date	2017-08-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: PAR-CLIP and streamlined small RNA cDNA library preparation protocol for the identification of RNA binding protein target sites

Benhalevy, Daniel / Aishe A. Sarshad / Hannah L. McFarland / Markus Hafner

Methods. 2017 Apr. 15, v. 118-119

2017

Abstract: The study of protein-RNA interactions is critical for our understanding of cellular processes and regulatory circuits controlled by RNA binding proteins (RBPs). Recent next generation sequencing-based approaches significantly promoted our understanding ... ...

Abstract	The study of protein-RNA interactions is critical for our understanding of cellular processes and regulatory circuits controlled by RNA binding proteins (RBPs). Recent next generation sequencing-based approaches significantly promoted our understanding of RNA biology and its importance for cell function. We present a streamlined protocol for Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP), a technique that allows for the characterization of RBP binding sites on target RNAs at nucleotide resolution and transcriptome-wide scale. PAR-CLIP involves irreversible UV-mediated crosslinking of RNAs labeled with photoreactive nucleosides to interacting proteins, followed by stringent purification steps and the conversion of crosslinked RNA into small RNA cDNA libraries compatible with next-generation sequencing. The defining hallmark of PAR-CLIP is a diagnostic mutation at the crosslinking site that is introduced into cDNA during the library preparation process. This feature allows for efficient computational removal of contaminating sequences derived from non-crosslinked fragments of abundant cellular RNAs. In the following, we present two different step-by-step procedures for PAR-CLIP, which differ in the small RNA cDNA library preparation procedure: (1) Standard library preparation involving gel size selections after each enzymatic manipulation, and (2) A modified PAR-CLIP procedure (“on-beads” PAR-CLIP), where most RNA manipulations including the necessary adapter ligation steps are performed on the immobilized RNP. This streamlined procedure reduces the protocol preparation time by three days compared to the standard workflow.
Keywords	binding sites ; cDNA libraries ; complementary DNA ; crosslinking ; gels ; high-throughput nucleotide sequencing ; mutation ; nucleosides ; precipitin tests ; RNA ; RNA-binding proteins
Language	English
Dates of publication	2017-0415
Size	p. 41-49.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1066584-5
ISSN	1095-9130 ; 1046-2023
ISSN (online)	1095-9130
ISSN	1046-2023
DOI	10.1016/j.ymeth.2016.11.009
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The nucleolus is the site for inflammatory RNA decay during infection

Taeyun A. Lee / Heonjong Han / Ahsan Polash / Seok Keun Cho / Ji Won Lee / Eun A. Ra / Eunhye Lee / Areum Park / Sujin Kang / Junhee L. Choi / Ji Hyun Kim / Ji Eun Lee / Kyung-Won Min / Seong Wook Yang / Markus Hafner / Insuk Lee / Je-Hyun Yoon / Sungwook Lee / Boyoun Park

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 18

Abstract: The nucleolus is the traditional site for ribosomal RNA biogenesis. Here, the authors find that the nucleolus is a site of inflammatory pre-mRNA turnover and elucidated how immune homeostasis can be maintained by controlling inflammatory gene expression. ...

Abstract	The nucleolus is the traditional site for ribosomal RNA biogenesis. Here, the authors find that the nucleolus is a site of inflammatory pre-mRNA turnover and elucidated how immune homeostasis can be maintained by controlling inflammatory gene expression.
Keywords	Science ; Q
Language	English
Publishing date	2022-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: LARP4 mRNA codon-tRNA match contributes to LARP4 activity for ribosomal protein mRNA poly(A) tail length protection

Sandy Mattijssen / Aneeshkumar G Arimbasseri / James R Iben / Sergei Gaidamakov / Joowon Lee / Markus Hafner / Richard J Maraia

eLife, Vol

2017 Volume 6

Abstract: Messenger RNA function is controlled by the 3' poly(A) tail (PAT) and poly(A)-binding protein (PABP). La-related protein-4 (LARP4) binds poly(A) and PABP. LARP4 mRNA contains a translation-dependent, coding region determinant (CRD) of instability that ... ...

Abstract	Messenger RNA function is controlled by the 3' poly(A) tail (PAT) and poly(A)-binding protein (PABP). La-related protein-4 (LARP4) binds poly(A) and PABP. LARP4 mRNA contains a translation-dependent, coding region determinant (CRD) of instability that limits its expression. Although the CRD comprises <10% of LARP4 codons, the mRNA levels vary >20 fold with synonymous CRD substitutions that accommodate tRNA dynamics. Separately, overexpression of the most limiting tRNA increases LARP4 levels and reveals its functional activity, net lengthening of the PATs of heterologous mRNAs with concomitant stabilization, including ribosomal protein (RP) mRNAs. Genetic deletion of cellular LARP4 decreases PAT length and RPmRNA stability. This LARP4 activity requires its PABP-interaction domain and the RNA-binding module which we show is sensitive to poly(A) 3'-termini, consistent with protection from deadenylation. The results indicate that LARP4 is a posttranscriptional regulator of ribosomal protein production in mammalian cells and suggest that this activity can be controlled by tRNA levels.
Keywords	wobble decoding ; mouse ; anticodon ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	500
Language	English
Publishing date	2017-09-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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