Article
Biology
Sarah R. Hansen, David S. White, Mark Scalf, Ivan R. Correa, Lloyd M. Smith, Aaron A. Hoskins, Jonathan P. Staley
Summary: This study investigated the pathway of 5' SS selection by purified yeast U1 snRNP using colocalization single-molecule spectroscopy. The results revealed a sequence-dependent, two-step mechanism for U1 to reversibly select 5' SS, providing a kinetic basis for how U1 may rapidly surveil nascent transcripts for 5' SS.
Article
Anesthesiology
Hua Huang, Shermaine Huiping Tay, Winanto Ng, Shi Yan Ng, Tuck Wah Soong
Summary: The study revealed that the exon 27 of human TRPA1 can be alternatively spliced into two variants, affecting the channel function. By manipulating the splicing factor SRSF1, alternative splicing within exon 27 can be promoted, leading to decreased TRPA1 activity.
Article
Biochemistry & Molecular Biology
Sara Espinosa, Francesca De Bortoli, Xueni Li, John Rossi, Marisa E. Wagley, Hei-Yong G. Lo, J. Matthew Taliaferro, Rui Zhao
Summary: This study reveals that human PRPF39 serves as an alternative splicing factor by recruiting U1 snRNP to weak 5' ss. Additionally, it is found that TIA1 and LUC7L isoforms also play roles in this process. The similarities between yeast and human U1 snRNP structures support the use of yeast U1 snRNP as a model for understanding human alternative splicing mechanisms.
Article
Biochemical Research Methods
Maximiliano Beckel, Bruno Kaufman, Marcelo Yanovsky, Ariel Chernomoretz
Summary: In this study, we used a regularized maximum entropy modeling approach to analyze the composition of 5' splice site sequences. By mining for non-trivial two-site correlations, we were able to identify characteristic coupling patterns in donor sequences of different eukaryotes. These patterns carried lineage information and could reflect differences in splicing regulation between plants and animals. Our findings suggest clade-specific features of splicing and provide insights into the evolutionary history associated with splicing mechanisms.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biochemical Research Methods
Aleksei Mironov, Stepan Denisov, Alexander Gress, Olga V. Kalinina, Dmitri D. Pervouchine
Summary: Tandem alternative splice sites (TASS) are a special class of alternative splicing events characterized by closely arranged splice sites. Our analysis of RNA-seq data from healthy human tissues expands the catalog of TASS, revealing tissue-specific expression, regulatory mechanisms, and impact on protein structure. The study suggests that both tissue-specific and cell-type-specific factors contribute to the regulation of miSS expression, with some affecting protein-protein interactions or protein core stability.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Yodfat Leader, Galit Lev Maor, Matan Sorek, Ronna Shayevitch, Maram Hussein, Ofir Hameiri, Luna Tammer, Jonathan Zonszain, Ifat Keydar, Dror Hollander, Eran Meshorer, Gil Ast
Summary: The study reveals that the upstream 5' splice sites remain associated with the transcription machinery during intron synthesis through U1 snRNP, facilitating the rapid splicing of introns.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Matyas Flemr, Michaela Schwaiger, Daniel Hess, Vytautas Iesmantavicius, Josip Ahel, Alex Charles Tuck, Fabio Mohn, Marc Buhler
Summary: Novel RNA-binding proteins, NRDE2 and CCDC174, directly bind to U1 snRNA and 5'SS sequences in mammals, facilitating the selection and processing of weak 5'SS sequences, thus promoting proper splice site choice and accurate pre-mRNA splicing.
Article
Multidisciplinary Sciences
Masao Takeuchi, Kikuko Takeuchi, Tomoyo Takai, Ritsuko Yamaguchi, Tetsushi Furukawa, Ken-ichi Akagi, Jun K. Takeuchi
Summary: GPC5, a heparan sulfate proteoglycan, is localized to multiple subcellular regions and colocalizes with FGFR, Rab11, and ARF6, implicating its involvement in regulating cell migration. The delivery of GPC5 to different cellular locations via recycling endosomes suggests its key role in FGF2-stimulated cell migration.
Article
Biochemical Research Methods
Jennifer Yihong Tan, Ana Claudia Marques
Summary: Pervasive enhancer transcription and splicing of enhancer-associated long noncoding RNAs (elncRNAs) play crucial roles in enhancer activity and gene expression regulation. Our study reveals that the splicing motifs within multi-exonic elncRNAs have evolved under selective constraints during human evolution. Using a genome-wide approach, we provide evidence that elncRNA splicing is associated with chromatin signatures at enhancers and target mRNA expression. Our findings demonstrate the importance of efficient elncRNA splicing in enhancer activity.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Li Huang, Guangnan Li, Chen Du, Yu Jia, Jiayi Yang, Weiliang Fan, Yong-Zhen Xu, Hong Cheng, Yu Zhou
Summary: This study reveals that the polyA tail of mRNA acts as a splicing enhancer for the last intron via the nuclear polyA binding protein PABPN1. PABPN1 interacts with RBMs protein and recruits RBM26&27 to promote splicing. Furthermore, this splicing regulation is conserved in mice.
Article
Engineering, Environmental
Lin Qiao, Lirong Gao, Di Huang, Yang Liu, Chi Xu, Da Li, Minghui Zheng
Summary: In this study, a comprehensive analysis method was used to study complex harmful compounds in ambient air. Active compounds with biological effects were identified, providing new insights into pollutant priority control and clinical therapeutic strategies.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2022)
Editorial Material
Rheumatology
Robert Phillips
Summary: New research reveals the association between one of the two main isoforms of human FOXP3 transcription factor and inflammatory transcriptional regulation as well as autoimmunity.
NATURE REVIEWS RHEUMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Atsushi Sato, Hachidai Aizawa, Tetsuhiro Tsujino, Kazushige Isobe, Taisuke Watanabe, Yutaka Kitamura, Tomoyuki Kawase
Summary: A cytochemical method was established to visualize polyP in platelets reliably, with the optimal conditions determined. This method is useful for determining the distribution and amount of polyP in platelets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Psychiatry
Rasmon Kalayasiri, Kanokwan Dadwat, Supaksorn Thika, Sunee Sirivichayakul, Michael Maes
Summary: There are only a few studies on the immunological profiles of methamphetamine use, dependence, and induced psychosis. This study found that long-term methamphetamine use has a strong immunosuppressive impact on all immunological profiles. Methamphetamine use is associated with a combination of suppressed immune response and increased pro-inflammatory cytokines. Methamphetamine dependence is linked to increased immunosuppression and decreased stem cell factor levels. Methamphetamine-induced psychosis is related to significant decreases in all immunological profiles and increased pro-inflammatory cytokine signaling. The widespread immunosuppression caused by methamphetamine use may increase the risk of infectious and immune-related diseases.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Norika Liu, Naofumi Kawahira, Yasuhiro Nakashima, Haruko Nakano, Akiyasu Iwase, Yasunobu Uchijima, Mei Wang, Sean M. Wu, Susumu Minamisawa, Hiroki Kurihara, Atsushi Nakano
Summary: This study reveals that the Nkx2-5/Notch/RA signaling pathway is crucial for macrophage differentiation and that a subset of endocardial cells gives rise to hematopoietic cells, which are important for the formation of cardiac valves.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Haneen Daralnakhla, Osama Saher, Susanna Zamolo, Safa Bazaz, Jeremy P. Bost, Marc Heitz, Karin E. Lundin, Samir El Andaloussi, Tamis Darbre, Jean-Louis Reymond, Rula Zain, C. I. Edvard Smith
Summary: This study examined 18 peptide dendrimers conjugated to lipophilic moieties for transfection of single strand splice-switching oligonucleotides (ONs). 3rd generation peptide dendrimers with D-amino acid configuration showed superior transfection efficacy compared to L-form, increasing correction levels up to 93-fold with minimal toxicity. The findings suggest that lipid-conjugated, D-amino acid-containing peptide dendrimers have the potential to be an effective and safe delivery vector for splice-switching ONs.
Article
Oncology
H. Yesid Estupinan, Qing Wang, Anna Berglof, Gerard C. P. Schaafsma, Yuye Shi, Litao Zhou, Dara K. Mohammad, Liang Yu, Mauno Vihinen, Rula Zain, C. I. Edvard Smith
Summary: Certain double mutants were found to be super-resistant to irreversible inhibitors, while reversible inhibitors showed variable patterns from resistance to no resistance, collectively demonstrating the structural constraints for different classes of inhibitors that may affect their clinical application.
Article
Oncology
Lisa Blixt, Gordana Bogdanovic, Marcus Buggert, Yu Gao, Sophia Hober, Katie Healy, Hemming Johansson, Christian Kjellander, Sara Mravinacova, Sandra Muschiol, Peter Nilsson, Marzia Palma, Elisa Pin, C. I. Edvard Smith, Olga Stromberg, Margaret Sallberg Chen, Rula Zain, Lotta Hansson, Anders Osterborg
Summary: The study revealed that severe cases of Covid-19 were equally distributed among CLL patients, regardless of age, gender, BMI, or CLL status, except for the Cumulative Illness Rating Scale (CIRS). The mortality rate was higher in patients aged 75 and above. Despite the high hospitalization rate, there was a numerical reduction in deaths and ICU admissions during different periods of the pandemic. Most convalescent patients showed robust and durable B and/or T cell immunity, with a majority testing positive for anti-SARS-CoV-2 antibodies even six to twelve months after infection.
Article
Biochemistry & Molecular Biology
Angelica Cuapio, Caroline Boulouis, Iva Filipovic, David Wullimann, Tobias Kammann, Tiphaine Parrot, Puran Chen, Mira Akber, Yu Gao, Quirin Hammer, Benedikt Strunz, Andre Perez Potti, Olga Rivera Ballesteros, Joshua Lange, Jagadeeswara Rao Muvva, Peter Bergman, Ola Blennow, Lotta Hansson, Stephan Mielke, Piotr Nowak, Gunnar Soderdahl, Anders Osterborg, C. I. Edvard Smith, Gordana Bogdanovic, Sandra Muschiol, Fredrika Hellgren, Karin Lore, Michal J. Sobkowiak, Giorgio Gabarrini, Katie Healy, Margaret Sallberg Chen, Evren Alici, Niklas K. Bjorkstrom, Marcus Buggert, Per Ljungman, Johan K. Sandberg, Soo Aleman, Hans-Gustaf Ljunggren
Summary: This study characterized NK cells in healthy individuals and immunocompromised patients during the course of an anti-SARS-CoV-2 BNT162b2 mRNA vaccine trial. The results showed that NK cell numbers, frequencies, subsets, phenotypes, and function remained unchanged following vaccination. Furthermore, a positive correlation was observed between the frequency of a specific type of NK cells at baseline and the antibody titers after vaccination.
MOLECULAR MEDICINE
(2022)
Article
Genetics & Heredity
Ola Hammarsten, Anna Lyytikainen, Sofia Thunstrom, Torben Ek, Anders Fasth, Olov Ekwall, Sara Cajander, Emilie Wahren Borgstrom, C. I. Edvard Smith, Pegah Johansson
Summary: This study successfully measured the sensitivity of patient cells to DNA-damaging agents using an in vitro assay and found associations between different DNA repair gene variants and cell sensitivity.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Biochemistry & Molecular Biology
D. Alexieva, Y. Long, R. Sarkar, H. Dhayan, E. Bruet, Rm Winston, I Vorechovsky, L. Castellano, N. J. Dibb
Summary: Mutations of splice sites, auxiliary splicing elements, and the splicing machinery can cause a wide range of genetic diseases. Background splicing information can predict the complex effects of splice mutations, including cryptic splice activation and single or multiple exon skipping. Comparison of known background splicing information with human splice site mutation databases can effectively predict the impact of splice site mutations.
Article
Engineering, Biomedical
Jeremy P. Bost, Osama Saher, Daniel Hagey, Doste R. Mamand, Xiuming Liang, Wenyi Zheng, Giulia Corso, Oskar Gustafsson, Andre Gorgens, Ci Edvard Smith, Rula Zain, Samir El Andaloussi, Dhanu Gupta
Summary: Extracellular vesicles (EVs) are nanosized cell-derived vesicles that facilitate intercellular communication via transmitting biological cargo. The production of EVs is influenced by various pathways and external factors in the cell media, with ceramide-dependent pathway being a major contributor to engineered EV production. The study provides insights into understanding and optimizing EV production in cell culture for developing advanced methods.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Reuben J. Pengelly, Dara Bakhtiar, Ivana Borovska, Jana Kralovicova, Igor Vorechovsky
Summary: Auxilliary splicing sequences in exons, known as enhancers (ESEs) and silencers (ESSs), have undergone strong selection pressures. The exonic sequences encoding calcium-binding residues show higher levels of exon inclusion, indicating their high retention capacity during eukaryotic evolution.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Immunology
Carl Inge Edvard Smith, Rula Zain, Anders osterborg, Marzia Palma, Marcus Buggert, Peter Bergman, Yenan Bryceson
Summary: The scarcity of plasmacytoid dendritic cells (pDCs) in patients with chronic lymphocytic leukaemia (CLL) may contribute to the severe clinical course of COVID-19 in these patients. Treatment of CLL with Bruton's tyrosine kinase (BTK) inhibitors can increase the number of pDCs.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Neurosciences
Igor Vorechovsky
Summary: Olduvai protein domains have experienced the greatest increase in copy number of any coding region in the human genome and are associated with brain volume, neuron count, cognitive abilities, and disorders of the autistic spectrum. Research shows that the inclusion of Olduvai exon doublets in mature transcripts is facilitated by a potent splicing enhancer created through duplication within the first exon, safeguarding the expanded Olduvai exon doublets in the mature transcriptome.
Article
Endocrinology & Metabolism
Per-Ola Carlsson, Daniel Espes, Sofia Sisay, Lindsay C. Davies, C. I. Edvard Smith, Mathias G. Svahn
Summary: This study aimed to investigate the safety and efficacy of treatment with allogeneic Wharton's jelly-derived mesenchymal stromal cells (MSCs) in recent-onset type 1 diabetes. Results showed that treatment with ProTrans resulted in smaller decline in C-peptide levels and no change in insulin requirements, suggesting the potential to preserve beta cell function.
Article
Biochemistry & Molecular Biology
Ivana Borovska, Igor Vorechovsky, Jana Kralovicova
Summary: Transcriptomic diversity in primates was expanded by exonizations of intronic Alu elements. RNA conformation changes rather than splicing regulatory motifs were found to better predict the splicing outcome. SRP9/14 heterodimer was shown to be involved in the splicing regulation of Alu-derived exons. Nucleotide substitutions during primate evolution relaxed the conserved left-arm AluJ structure and reduced the capacity of SRP9/14 to stabilize the closed Alu conformation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Dara Bakhtiar, Katarina Vondraskova, Reuben J. Pengelly, Martin Chivers, Jana Kralovicova, Igor Vorechovsky
Summary: This study investigates the splicing codes of human exons encoding two essential divalent metals. The results show that exons encoding Zn2+-coordinating amino acids are less supported by auxiliary splicing motifs compared to exons coordinating Ca2+, but are compensated by other mechanisms to ensure sufficient splicing and metalloprotein expression.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Medicine, Research & Experimental
Katie Healy, Elisa Pin, Puran Chen, Gunnar Soderdahl, Piotr Nowak, Stephan Mielke, Lotta Hansson, Peter Bergman, C. I. Edvard Smith, Per Ljungman, Davide Valentini, Ola Blennow, Anders Osterborg, Giorgio Gabarrini, Khaled Al-Manei, Hassan Alkharaan, Michal Jacek Sobkowiak, Jamil Yousef, Sara Mravinacova, Angelica Cuapio, Xinling Xu, Mira Akber, Karin Lore, Cecilia Hellstrom, Sandra Muschiol, Gordana Bogdanovic, Marcus Buggert, Hans-Gustaf Ljunggren, Sophia Hober, Peter Nilsson, Soo Aleman, Margaret Sallberg Chen
Summary: This study found that the mRNA BNT162b2 vaccine can induce immune responses in the saliva of immunocompromised individuals to SARS-CoV-2 spike antigens. Salivary responses were correlated with specific IgG titers and neutralizing capacity in serum, and had a high predictive power for identifying vulnerable groups for revaccination.