Article
Genetics & Heredity
Young Hoon Jung, Jay Jiyong Kwak, Kwangsic Joo, Hyuk Jun Lee, Kyu Hyung Park, Min Seok Kim, Eun Kyoung Lee, Suk Ho Byeon, Christopher Seungkyu Lee, Jinu Han, Junwon Lee, Chang Ki Yoon, Se Joon Woo
Summary: This study investigated the clinical features, natural course, and genetic characteristics of Koreans with rhodopsin-associated retinitis pigmentosa (RHO-associated RP). The study found that the generalized RP group had a higher rate of visual field impairment progression to late-stage RP compared to the sector RP group. Best-corrected visual acuity deterioration was observed only in the generalized RP group. The study also identified several RHO gene mutations, including some that presented with both generalized and sector RP phenotypes.
FRONTIERS IN GENETICS
(2023)
Article
Genetics & Heredity
Liliya Nazlamova, Suly Saray Villa Vasquez, Jenny Lord, Varshini Karthik, Man-Kim Cheung, Jorn Lakowski, Gabrielle Wheway
Summary: Retinitis pigmentosa (RP) is a common hereditary cause of blindness, and understanding its molecular mechanism is important for targeted treatment. This study used various experimental methods and data analysis to confirm that mutations in certain genes associated with RP can lead to defects in microtubules, centrosomes, and cilia in cells, triggering differential splicing of DNA damage response pathways. Additionally, the study identified the TTLL3 gene as a potential therapeutic target, as it plays a crucial role in the cilial tubulin glycylation process.
FRONTIERS IN GENETICS
(2022)
Review
Genetics & Heredity
Katherine A. Wood, Megan A. Eadsforth, William G. Newman, Raymond T. O'Keefe
Summary: Pre-mRNA splicing is carried out by the spliceosome, a complex molecular machinery comprised of various proteins and small nuclear ribonucleoprotein complexes. Genetic variants affecting splicing factors can lead to human diseases such as retinitis pigmentosa, craniofacial disorders, and cancer. While the roles of U5 snRNP proteins in different diseases have been defined, the mechanisms underlying tissue specificity in disease phenotypes remain unclear.
FRONTIERS IN GENETICS
(2021)
Review
Multidisciplinary Sciences
Ammanie Abdul-Fatah, Leila Esmaeilisaraji, Crisel Mae Juan, Martin Holcik
Summary: This paper provides support for the creation of a mitochondrial disease patient registry in Canada through a systematic scoping review. It also fills a knowledge gap by providing a narrative synthesis of published literature on these registries.
Article
Neurosciences
Angeles Arzalluz-Luque, Jose Luis Cabrera, Heli Skottman, Alberto Benguria, Arantxa Bolinches-Amoros, Nicolas Cuenca, Vincenzo Lupo, Ana Dopazo, Sonia Tarazona, Barbara Delas, Miguel Carballo, Beatriz Pascual, Imma Hernan, Slaven Erceg, Dunja Lukovic
Summary: Retinitis pigmentosa is a rare progressive disease with no current therapeutic options. A study found that mutations in splicing factor PRPF8 lead to changes in splice site selection and exon inclusion, affecting retinal cell functions and specificity, offering a framework for novel therapeutic opportunities.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Laura Kuehlewein, Ditta Zobor, Katarina Stingl, Melanie Kempf, Fadi Nasser, Antje Bernd, Saskia Biskup, Frans P. M. Cremers, Muhammad Imran Khan, Pascale Mazzola, Karin Schaeferhoff, Tilman Heinrich, Tobias B. Haack, Bernd Wissinger, Eberhart Zrenner, Nicole Weisschuh, Susanne Kohl
Summary: This study investigated the phenotypic and genotypic features of retinitis pigmentosa associated with PDE6B gene variants, with most mutations being splicing defects and missense mutations. 43% of the PDE6B variants found in patients were novel, contributing to the mutation spectrum of PDE6B.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, General & Internal
Abinaya Thenappan, Arjun Nanda, Chang Sup Lee, Sun Young Lee
Summary: Timely recognition and differentiation of pseudo-RP cases is crucial due to the treatable nature of many such conditions. This review provides examples of pseudo-RP cases and an in-depth overview of RP masquerades, emphasizing the importance of accurate diagnoses for effective interventions. It also discusses the role of genetic testing in RP patients and highlights the necessity of a precise clinical assessment for diagnosis and management.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Dongju Won, Joo-Yeon Hwang, Yeeun Shim, Suk Ho Byeon, Junwon Lee, Christopher Seungkyu Lee, Min Kim, Hyun Taek Lim, Jong Rak Choi, Seung-Tae Lee, Jinu Han
Summary: MEIs are often missed due to exceeding read lengths of short-read sequencing technologies, but a grep search program was developed in this study to efficiently detect the RP1 Alu insertion. The Alu insertion in RP1 exon 4 was found to be a common founder mutation in Korean population.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Pankhuri Gupta, Kenji Nakamichi, Alyssa C. C. Bonnell, Ryan Yanagihara, Nick Radulovich, Fuki M. M. Hisama, Jennifer R. R. Chao, Debarshi Mustafi
Summary: Phasing genetic variants is crucial for identifying potential disease-causing variants. Reclassification of variants of uncertain significance (VUS) in autosomal recessive inherited retinal diseases (IRDs) can lead to a genetic diagnosis when combined with familial co-segregation analysis. This study reports four cases where a VUS was found to be trans to a known pathogenic variant through familial co-segregation, resulting in the reclassification of the VUS to likely pathogenic and a genetic diagnosis. Additionally, targeted long-read sequencing was utilized to infer variant phasing in a simplex patient without access to family members for co-segregation analysis. This emerging method provides a solution for cases where genetic testing of family members is unfeasible, allowing for a complete genetic diagnosis.
NPJ GENOMIC MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Christine Voessing, Paul Atigbire, Jannis Eilers, Fenja Markus, Knut Stieger, Fei Song, John Neidhardt
Summary: This study identifies distinct functional properties of major RPGR isoforms, despite their similar subcellular localization. A tissue-specific expression ratio between RPGR(skip14/15) and RPGR(ex1-19) seems required to regulate the ciliary concentration of RPGR interaction partners.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Daniel J. Jackson, Adam M. Dubis, Mariya Moosajee
Summary: This study reports the natural history of CNGB1-related RP and finds that it is a slowly progressive disease with patients maintaining visual acuity. Further research is needed to determine the clinical endpoints to be used in clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Ophthalmology
Jacque L. Duncan, Peiyao Cheng, Maureen G. Maguire, Allison A. Ayala, David G. Birch, Janet K. Cheetham, Todd A. Durham, Abigail T. Fahim, Carel B. Hoyng, Hiroshi Ishikawa, Michel Michaelides, Mark E. Pennesi, Jose-Alain Sahel, Katarina Stingl, Christina Y. Weng
Summary: A prospective observational study was conducted on 102 patients with USH2A-related retinal degeneration over a period of two years. It was found that quantitative measures of static perimetry significantly declined during this time. The greatest changes were observed in the full field and peripheral vision, while the central vision showed the least change.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Biology
Mei Nakahara, Akio Oishi, Manabu Miyata, Hanako Ohashi Ikeda, Tomoko Hasegawa, Shogo Numa, Yuki Otsuka, Maho Oishi, Fumihiko Matsuda, Akitaka Tsujikawa
Summary: Concentric retinitis pigmentosa is a rare form of RP with better visual function, preserved ellipsoid zones, and subnormal but recordable responses on electroretinogram. Genetic testing may reveal different causative genes in patients with this condition. Myotonic dystrophy-associated retinopathy is an important differential diagnosis to consider.
Article
Biochemistry & Molecular Biology
Catiana H. Cartwright-Acar, Kenneth Osterhoudt, Jessie M. N. G. L. Suzuki, Destiny R. Gomez, Sol Katzman, Alan M. Zahler
Summary: The spliceosome undergoes extensive rearrangements during assembly onto precursor messenger RNAs, with multiple interactions at different stages responsible for maintaining the initial 5' splice site identified by U1snRNA. Through a genetic screen, new suppressor alleles have been identified, which affect specific native alternative 5' splice sites. This study indicates the complexity of spliceosome assembly and the role of various components in maintaining accurate splicing events.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Ophthalmology
Laura Kuehlewein, Torsten Strasser, Gunnar Blumenstock, Katarina Stingl, M. Dominik Fischer, Barbara Wilhelm, Eberhart Zrenner, Bernd Wissinger, Susanne Kohl, Nicole Weisschuh, Ditta Zobor
Summary: This study describes the natural course of disease progression in patients with PDE6A-associated arRP, and establishes a detailed genotype-phenotype correlation. The severity of different disease-causing PDE6A mutations in humans with respect to central visual function was ranked, and the small annual decline rates in central retinal function may pose challenges in assessing treatment efficacy in interventional trials.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Adriana Roithova, Klara Klimesova, Josef Panek, Cindy L. Will, Reinhard Luehrmann, David Stanek, Cyrille Girard
NUCLEIC ACIDS RESEARCH
(2018)
Article
Biochemistry & Molecular Biology
Jana Kralovicova, Ivana Sevcikova, Eva Stejskalova, Mina Obuca, Michael Hiller, David Stanek, Igor Vorechovsky
NUCLEIC ACIDS RESEARCH
(2018)
Article
Biochemistry & Molecular Biology
Zuzana Krchnakova, Prasoon Kumar Thakur, Michaela Krausova, Nicole Bieberstein, Nejc Haberman, Michaela Mueller-McNicoll, David Stanek
NUCLEIC ACIDS RESEARCH
(2019)
Article
Multidisciplinary Sciences
Adriana Roithova, David Stanek
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2019)
Article
Biochemistry & Molecular Biology
Adriana Roithova, Zuzana Feketova, Stepanka Vanacova, David Stanek
NUCLEIC ACIDS RESEARCH
(2020)
Review
Biochemical Research Methods
David Stanek
Summary: This review focuses on the role of splicing in the life of long non-coding RNA (lncRNA), summarizing differences in splicing efficiency between protein-coding genes and lncRNAs. The discussion also highlights the conservation of splice sites in lncRNAs and suggests additional roles splicing may play in lncRNA metabolism. The hypothesis that splicing machinery can protect cells from undesired transcripts is also explored.
Article
Multidisciplinary Sciences
Klara Klimesova, Jitka Vojackova, Nenad Radivojevic, Franck Vandermoere, Edouard Bertrand, Celine Verheggen, David Stanek
Summary: The study revealed that TSSC4 is a component of U5 snRNP and plays a critical role in promoting tri-snRNP formation, providing new insights into the biogenesis and recycling process of spliceosomal U5 snRNP.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Davide A. Basello, A. Gregory Matera, David Stanek
Summary: This study reports an amino acid substitution found in a widely-used EGFP-coilin construct that has a dominant-negative effect on Cajal body formation. The results show that a mutation in the C-terminal region of human coilin can disrupt the assembly of Cajal bodies.
JOURNAL OF CELL SCIENCE
(2022)
Article
Multidisciplinary Sciences
Mina Obuca, Zuzana Cvackova, Jan Kubovciak, Michal Kolar, David Stanek
Summary: This study analyzed the role of RNA helicase DHX38 in retinitis pigmentosa (RP). The findings showed that DHX38 is associated with key splicing factors, regulates alternative splicing and promotes the usage of cryptic splice sites. The RP-linked substitution G332D modulates DHX38's splicing activity.
Article
Multidisciplinary Sciences
Zuzana Cihlarova, Jan Kubovciak, Margarita Sobol, Katerina Krejcikova, Jana Sachova, Michal Kolar, David Stanek, Cyril Barinka, Grace Yoon, Keith W. Caldecott, Hana Hanzlikova
Summary: Mutations in BRAT1 are associated with neurodevelopmental delay and neurodegeneration. This study reveals that BRAT1 is a component of Integrator and plays a crucial role in the processing of specific RNAs. The authors also demonstrate that patient-derived cells with BRAT1 mutations show reduced levels of the Integrator catalytic subunit and impaired RNA processing.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Klara Klimesova, Hana Petrzilkova, Cyril Barinka, David Stanek
Summary: SART3 is a multifunctional protein involved in multiple steps of gene expression, including the assembly and recycling of the spliceosomal U4/U6 snRNP. This study demonstrates that SART3 interacts with the 12S U2 snRNP through its N-terminal HAT domain. Furthermore, it associates with the post-splicing complex containing U2 and U5 snRNP components, and also interacts with the RNA helicase DHX15. The proposed model suggests that SART3 protects and initiates the recycling of U6 snRNA in the post-splicing complex.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biology
Michaela Krausova, Michaela Kreplova, Poulami Banik, Zuzana Cvackova, Jan Kubovciak, Martin Modrak, Dagmar Zudova, Jiri Lindovsky, Agnieszka Kubik-Zahorodna, Marcela Palkova, Michal Kolar, Jan Prochazka, Radislav Sedlacek, David Stanek
Summary: A subset of RP patients have mutations in spliceosomal components, including the PRPF8 protein. Two alleles of murine Prpf8 were created to mimic these aberrant PRPF8 mutations. Homozygous mice expressing the aberrant Prpf8 variants developed progressive cerebellar atrophy due to granule cell loss, and circRNAs were deregulated in their cerebellum. The down-regulation of splicing proteins coincided with neurodegeneration onset and was more pronounced in mouse strains expressing mutated Prpf8. These findings suggest that the deregulation of circRNAs triggers neuronal death in RP patients.
LIFE SCIENCE ALLIANCE
(2023)
Article
Multidisciplinary Sciences
Josef Panek, Adriana Roithova, Nenad Radivojevic, Michal Sykora, Archana Bairavasundaram Prusty, Nicholas Huston, Han Wan, Anna Marie Pyle, Utz Fischer, David Stanek
Summary: This study reveals that pre-snRNAs have compact structures that prevent binding with Sm proteins during spliceosomal snRNP maturation. Gemin3 and Gemin4 are necessary for rearranging pre-snRNAs to allow interaction with Sm proteins.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
David Stanek
Summary: The nucleus of higher eukaryotes contains structures that concentrate specific biomolecules and play various roles in nuclear metabolism. This review focuses on coilin and Cajal bodies, which are involved in the metabolism of non-coding nuclear RNAs. However, there is still limited understanding of the structure and function of coilin, and a comprehensive model for the origin of Cajal bodies is lacking. Recent results on Cajal bodies and coilin are summarized and discussed in the context of previous research in this field.
Article
Cell Biology
Tomas Zelenka, Dionysios-Alexandros Papamatheakis, Petros Tzerpos, Giorgos Panagopoulos, Konstantinos C. Tsolis, Vassilis M. Papadakis, Dimitris Mariatos Metaxas, George Papadogkonas, Eleftherios Mores, Manouela Kapsetaki, Joseph Papamatheakis, David Stanek, Charalampos Spilianakis
Summary: In this report, the regulatory actions of SATB1 genome organizer in intra-thymic T cell development were explored. The study found that both transcription and splicing were deregulated in Satb1 knockout murine thymocytes. Moreover, a novel SATB1 protein isoform with distinct biophysical behavior was characterized, suggesting potential functional differences compared to the commonly studied isoform.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)