Article
Genetics & Heredity
Kang Xie, Baitao Zeng, Liuyang Zhang, Shaohong Chen, Yongyi Zou, Huizhen Yuan, Shuhui Huang, Feng Wang, Qing Lu, Yanqiu Liu, Bicheng Yang
Summary: This study aimed to investigate the mutational spectrum of the PTS gene in patients with PTPSD from Jiangxi province. The results revealed 106 variants in 106 alleles of 53 patients, including 13 previously reported variants and two novel variants. The most common variant was c.259C > T, followed by c.84-291A > G, c.155A > G, c.286G > A, and c.379C > T. The findings not only provide guidance for the molecular diagnosis and genetic counseling in cases of PTPS deficiency but also enrich the PTS mutation database.
FRONTIERS IN GENETICS
(2022)
Article
Medicine, Research & Experimental
Nino Kraveishvili, Eka Kvaratskhelia, Sandro Surmava, Merab Kvintradze, Maia Zarandia, Tinatin Gorgiladze, Elene Abzianidze
Summary: This study analyzed the methylation status of LINE-1 and Alu repetitive elements in peripheral blood mononuclear cells (PBMCs) from patients with migraine compared to healthy control subjects. The results showed higher levels of unmethylated cytosines in both LINE-1 and Alu repetitive elements in the migraine group. Furthermore, a significant difference was found in the methylation level of LINE-1 between the TT and CC genotype groups of the methylenetetrahydrofolate reductase gene.
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
(2023)
Article
Endocrinology & Metabolism
Drago Bratkovic, Lali Margvelashvili, Michel C. Tchan, Janelle Nisbet, Neil Smith
Summary: In this study, the researchers compared the effects of PTC923 and sapropterin on blood phenylalanine levels. The results showed that PTC923 was more effective in reducing blood phenylalanine levels, especially at higher doses (60 mg/kg), and had a faster onset of action.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2022)
Review
Endocrinology & Metabolism
Nastassja Himmelreich, Nenad Blau, Beat Thoeny
Summary: Tetrahydrobiopterin (BH4) deficiency, caused by genetic variants in genes involved in cofactor biosynthesis and recycling, leads to reduced cofactor levels and potential systemic hyperphenylalaninemia and neurological sequelae. The clinical impact of these genetic variants vary and are crucial for genetic counseling and precision medicine development.
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Oncology
Naohiko Akimoto, Melissa Zhao, Tomotaka Ugai, Rong Zhong, Mai Chan Lau, Kenji Fujiyoshi, Junko Kishikawa, Koichiro Haruki, Kota Arima, Tyler S. Twombly, Xuehong Zhang, Edward L. Giovannucci, Kana Wu, Mingyang Song, Andrew T. Chan, Yin Cao, Jeffrey A. Meyerhardt, Kimmie Ng, Marios Giannakis, Juha P. Vayrynen, Jonathan A. Nowak, Shuji Ogino
Summary: The study reveals that tumor LINE-1 hypomethylation becomes increasingly common with decreasing age of colorectal cancer diagnosis, which suggests a role of global DNA hypomethylation in colorectal cancer arising in younger adults and is associated with higher colorectal cancer-specific mortality.
Article
Cell Biology
Neha Sarodaya, Apoorvi Tyagi, Hyun-Jin Kim, Jencia Carminha Colaco, Ju-Seop Kang, Woo Jin Kim, Kye-Seong Kim, Suresh Ramakrishna
Summary: This study identified the role of USP19 in regulating PAH protein stability and promoting its metabolic activity.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Article
Medicine, General & Internal
Yu Rim Lee, Gyeonghwa Kim, Hye Won Lee, Won Young Tak, Soo Young Park, Se Young Jang, Young Oh Kweon, Jung Gil Park, Young Seok Han, Jae Min Chun, Ja Ryung Han, Keun Hur
Summary: In patients with hepatocellular carcinoma (HCC), LINE-1 hypomethylation was found to be an independent risk factor for poor prognosis, potentially influencing tumor development by activating oncogenes. Additionally, the expression of suppression of tumorigenicity 18 was correlated with LINE-1 methylation levels and may play a role in the development of HCC.
Article
Biochemistry & Molecular Biology
Yubo Cheng, Luke Saville, Babita Gollen, Ana Alvarez Veronesi, Majid Mohajerani, Jeffrey T. Joseph, Athanasios Zovoilis
Summary: Research has shown that non-coding RNAs produced by SINE elements play a significant role in the pathogenesis of Alzheimer's disease, controlling gene expression and exhibiting a pattern of deregulation in the brains of AD patients.
Article
Genetics & Heredity
Xin Wang, Yanyun Wang, Dingyuan Ma, Zhilei Zhang, Yahong Li, Peiying Yang, Yun Sun, Tao Jiang
Summary: This study investigated the prevalence, mutational and phenotypic spectrum, and prognosis of HPA in Nanjing, Jiangsu Province, China through neonatal screening from January 2001 to September 2020. A total of 181 patients were diagnosed with HPA from 1 to 957 newborns, with an incidence of 1:6873. The study identified common mutations in PAH and BH4 deficient patients, providing valuable information for genetic counseling and management of future cases.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Biotechnology & Applied Microbiology
Guangjie Han, Nan Zhang, Heng Jiang, Xiangkun Meng, Kun Qian, Yang Zheng, Jian Xu, Jianjun Wang
Summary: Lepidopteran insect genomes contain a diversity of SINEs, with significant variation in retrotransposition activity and copy number between host lineages and SINE lineages. Host-parasite interactions facilitate horizontal transfer of SINEs between baculovirus and its lepidopteran hosts.
Article
Multidisciplinary Sciences
Oscar Aubi, Karina S. Prestegard, Kunwar Jung-KC, Tie-Jun Sten Shi, Ming Ying, Ann Kari Grindheim, Tanja Scherer, Arve Ulvik, Adrian McCann, Endy Spriet, Beat Thony, Aurora Martinez
Summary: Phenylketonuria (PKU) is caused by autosomal recessive variants in phenylalanine hydroxylase (PAH) and can lead to neurotoxicity. Here the authors describe a mouse model of PKU based on a mutation in phenylalanine hydroxylase (R261Q) which replicates traits of this disease and shows a proteostasis defect and oxidative stress, implying a gain-of-function contribution to the disease phenotype.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Woo Ryung Kim, Eun Gyung Park, Hee-Eun Lee, Sang-Je Park, Jae-Won Huh, Jeong Nam Kim, Heui-Soo Kim
Summary: The study reveals that Hsa-miR-422a, derived from SINE, can regulate the expression of the ARID5B gene through its interaction with TF and NF-E2.
MOLECULES AND CELLS
(2021)
Article
Pediatrics
Haruo Shintaku, Toshihiro Ohura, Masaki Takayanagi, Shigeo Kure, Misao Owada, Yoichi Matsubara, Makoto Yoshino, Yoshiyuki Okano, Tetsuya Ito, Torayuki Okuyama, Kimitoshi Nakamura, Masafumi Matuo, Fumio Endo, Hiroyuki Ida
Summary: The importance of sapropterin hydrochloride for the treatment of tetrahydrobiopterin-responsive hyperphenylalaninemia is highlighted, with recommendations to diagnose through tetrahydrobiopterin administration tests instead of relying on phenotype or blood phenylalanine levels. Treatment with sapropterin hydrochloride is feasible for all ages in cases of tetrahydrobiopterin-responsive hyperphenylalaninemia, and further investigation is needed despite reported efficacy and safety in preventing maternal phenylketonuria.
PEDIATRICS INTERNATIONAL
(2021)
Article
Multidisciplinary Sciences
Fumio Takahashi, Chenyang Zhang, Hirohiko Hohjoh, Ben Raveney, Takashi Yamamura, Nobuhiro Hayashi, Shinji Oki
Summary: The study reveals the accumulation of Eomes + Th cells in the CNS of mouse models of neurodegenerative diseases, which secrete neurotoxic granzyme B after encountering with ORF1 antigen. Multimodal derepression of neuronal L1 transcription in EAE and ALS/AD models sheds light on a previously unappreciated pathogenesis of neurodegeneration.
Article
Endocrinology & Metabolism
Kismet Ciki, Yilmaz Yildiz, Didem Yucel Yilmaz, Emine Pektas, Aysegul Tokatli, R. Koksal Ozgul, H. Serap Sivri, Ali Dursun
Summary: DNAJC12 deficiency, in addition to tetrahydrobiopterin deficiencies and phenylalanine hydroxylase deficiency, can account for 10% or more cases of unexplained hyperphenylalaninemia, with a broad phenotypic spectrum and possible beneficial effects from early diagnosis and treatment.
METABOLIC BRAIN DISEASE
(2021)
Article
Genetics & Heredity
Hesham M. Ismail, Navaneethakrishnan Krishnamoorthy, Nader Al-Dewik, Hatem Zayed, Nura A. Mohamed, Valeria Di Giacomo, Sapna Gupta, Johannes Haberle, Beat Thony, Henk J. Blom, Waren D. Kruger, Tawfeg Ben-Omran, Gheyath K. Nasrallah
Article
Oncology
Jana Kralovicova, Ivana Borovska, Monika Kubickova, Peter J. Lukavsky, Igor Vorechovsky
Article
Biochemistry & Molecular Biology
Maria Elena Vilar Alvarez, Martin Chivers, Ivana Borovska, Steven Monger, Eleni Giannoulatou, Jana Kralovicova, Igor Vorechovsky
Summary: TEs play a crucial role in shaping the evolution of exon-intron structure and have been linked to morbidity. This study investigates how recent TE invasions cooperate with older TEs in generating new coding sequences, identifying novel TE clusters that facilitate exon selection. By analyzing the RNA secondary structure and functional impact of mutations in exon-intron boundaries, the study sheds light on the formation and kinetics of pre-mRNA building blocks necessary for splice-site selection. The findings provide valuable insights into the fine-tuning of auxiliary splicing motifs and the regulation of aberrant splice-site activation.
Article
Biochemistry & Molecular Biology
Jana Kralovicova, Ivana Borovska, Reuben Pengelly, Eunice Lee, Pavel Abaffy, Radek Sindelka, Frank Grutzner, Igor Vorechovsky
Summary: The study reveals the mechanism by which Ca2+-sensitive and insensitive E1 subunits regulate tissue-specific NADH and ATP supply through different exons. Remote lariat branch points restrict intron length and prevent transposon insertions, with the expansion of dBPs in early terrestrial species.
NUCLEIC ACIDS RESEARCH
(2021)
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
Biochemistry & Molecular Biology
Dorothea Haas, Jana Hauke, Kathrin Schwarz, Lucia Consalvi, Friedrich K. Trefz, Nenad Blau, Georg F. Hoffmann, Peter Burgard, Sven F. Garbade, Juergen G. Okun
Summary: Monitoring phenylalanine concentrations is crucial for managing phenylketonuria. Variations in Phe concentrations between different blood sample types have been observed, with significantly lower Phe levels in erythrocytes compared to plasma. Reliable conversion of dried blood spots into plasma concentrations is essential for therapy recommendations.
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)
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
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)
Meeting Abstract
Biochemistry & Molecular Biology
M. Sekelska, J. Kralovicova, I. Sevcikova, A. Soltysova, B. Olsson, D. B. Asher, D. E. V. Pires, L. Ranganath, A. Zatkova
EUROPEAN JOURNAL OF HUMAN GENETICS
(2019)