Cited by Maf-family bZIP transcription factor NRL interacts with RNA-binding proteins and R-loops in retinal photoreceptors

Maf-family bZIP transcription factor NRL interacts with RNA-binding proteins and R-loops in retinal photoreceptors DOI

Ximena Corso‐Díaz,

Xulong Liang,

Kiam Preston

и другие.

Опубликована: Фев. 13, 2025

RNA-binding proteins (RBPs) perform diverse functions including the regulation of chromatin dynamics and coupling transcription with RNA processing. However, our understanding their actions in mammalian neurons remains limited. Using affinity purification, yeast-two-hybrid proximity ligation assays, we identified interactions multiple RBPs NRL, a Maf-family bZIP factor critical for retinal rod photoreceptor development function. In addition to splicing, many NRL-interacting are associated R-loops, which form during increase maturation. Focusing on DHX9 helicase, demonstrate that its expression is modulated by NRL NRL-DHX9 interaction positively influenced R-loops. ssDRIP-Seq analysis reveals both stranded unstranded R-loops at distinct genomic elements, characterized active inactive epigenetic signatures enriched neuronal genes. binds types suggesting an epigenetically independent Our findings suggest additional highlight complex among factors, RBPs, regulating gene retina.

Язык: Английский

Процитировано

Axonal motor polyneuropathy in a 13 years old Girl with a de Novo variant in ADNP DOI

Sara Scaccini,

Carlo Alberto Cesaroni, Stefano Giuseppe Caraffi

и другие.

Neurogenetics, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 24, 2025

Язык: Английский

Процитировано

Maf-family bZIP transcription factor NRL interacts with RNA-binding proteins and R-loops in retinal photoreceptors DOI

Ximena Corso Diaz,

Xulong Liang,

Kiam Preston

и другие.

eLife, Год журнала: 2025, Номер 13

Опубликована: Март 6, 2025

RNA-binding proteins (RBPs) perform diverse functions including the regulation of chromatin dynamics and coupling transcription with RNA processing. However, our understanding their actions in mammalian neurons remains limited. Using affinity purification, yeast-two-hybrid proximity ligation assays, we identified interactions multiple RBPs neural retina leucine (NRL) zipper, a Maf-family factor critical for retinal rod photoreceptor development function. In addition to splicing, many NRL-interacting are associated R-loops, which form during increase maturation. Focusing on DHX9 helicase, demonstrate that its expression is modulated by NRL NRL–DHX9 interaction positively influenced R-loops. ssDRIP-Seq analysis reveals both stranded unstranded R-loops at distinct genomic elements, characterized active inactive epigenetic signatures enriched neuronal genes. binds types suggesting an epigenetically independent Our findings suggest additional highlight complex among factors, RBPs, regulating gene retina.

Язык: Английский

Процитировано

GA4GH Phenopacket-Driven Characterization of Genotype-Phenotype Correlations in Mendelian Disorders DOI

Lauren Rekerle, Daniel Daniš, Filip Rehburg

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

ABSTRACT Comprehensively characterizing genotype-phenotype correlations (GPCs) in Mendelian disease would create new opportunities for improving clinical management and understanding biology. However, heterogeneous approaches to data sharing, reuse, analysis have hindered progress the field. We developed Genotype Phenotype Evaluation of Statistical Association (GPSEA), a software package that leverages Global Alliance Genomics Health (GA4GH) Phenopacket Schema represent case-level genetic about individuals. GPSEA applies an independent filtering strategy boost statistical power detect categorical GPCs represented by Human Ontology terms. additionally enables visualization continuous phenotypes, severity scores, survival such as age onset or manifestations. applied 85 cohorts with 6613 previously published individuals variants one 80 genes associated 122 diseases identified 225 significant GPCs, 48 having at least statistically GPC. These results highlight standardized representations scalable discovery disease.

Язык: Английский

Процитировано

Expression of DDX49 in breast cancer and its mechanism regulating the proliferation and metastasis of breast cancer cells DOI

Yuanbin Wang,

Lijun Yang,

Xiangli Li

и другие.

Growth Factors, Год журнала: 2025, Номер unknown, С. 1 - 11

Опубликована: Апрель 3, 2025

DEAD-box RNA helicase (DDX) is linked to the invasion, drug resistance, proliferation, and epithelial-mesenchymal transition of tumour cells. This study examined potential mechanisms DDX49 in breast cancer. The expression cancer tissues cells was evaluated. effects on migration apoptosis were proteins associated with JAK/STAT pathway examined. A xenograft model established. elevated cell lines. shDDX49 suppressed ability proliferate, invade, migrate, but promoted apoptosis. Conversely, overexpression exerted an opposite effect. activation JAK-STAT signalling inhibited by shDDX49. efficiently inhibits growth mice may hinder spread inhibiting pathway.

Язык: Английский

Процитировано

A longitudinal analysis of function annotations of the human proteome reveals consistently high biases DOI

An Phan, Parnal Joshi, Claus Kadelka

и другие.

Database, Год журнала: 2025, Номер 2025

Опубликована: Янв. 1, 2025

The resources required to study gene function are limited, especially when considering the number of genes in human genome and complexity their function. Therefore, prioritized for experimental studies based on many different considerations, including, but not limited to, perceived biomedical importance, such as disease-associated genes, or understanding biological processes, cell signalling pathways. At same time, most studied under-characterized, which hampers our potential effects health wellness. Understanding annotation disparity is a necessary first step toward how much functional knowledge gained from genome, guidelines better targeting future effectively. Here, we present comprehensive longitudinal analysis proteome utilizing data tools economics information theory. Specifically, view population proteins within economy: treat quantified protein's analogue wealth examine distribution manner societies. Our results show highly skewed about over last decade, inequality annotations given remains high. Additionally, correlation between protein captured databases interest reflected by mentions scientific literature. We large gap dissect factors leading this gap. In conclusion, shows that research efforts should be redirected less mitigate among both

Язык: Английский

Процитировано

DDX27: An RNA helicase regulating cancer progression and therapeutic prospects DOI

Yurong Zheng, Xinyi Chen, Yunfei Huang

и другие.

International Journal of Biological Macromolecules, Год журнала: 2025, Номер 313, С. 144388 - 144388

Опубликована: Май 19, 2025

Язык: Английский

Процитировано

MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature DOI

Remzi Karayol,

Maria Carla Borroto,

Sadegheh Haghshenas

и другие.

The American Journal of Human Genetics, Год журнала: 2024, Номер 111(7), С. 1330 - 1351

Опубликована: Май 29, 2024

Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit regulator and responsible for 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify cohort 25 individuals with heterozygous de novo variants MSL member MSL2. MSL2 were associated NDD phenotypes including global developmental delay, intellectual disability, hypotonia, motor issues such coordination problems, feeding difficulties, gait disturbance. Dysmorphisms behavioral and/or psychiatric conditions, autism spectrum disorder, lesser extent, seizures, connective tissue disease signs, sleep disturbance, vision other organ anomalies, observed affected individuals. As molecular biomarker, sensitive specific DNA methylation episignature been established. Induced pluripotent stem cells (iPSCs) derived from three members our exhibited reduced levels. Remarkably, while NDD-associated two the (MOF MSL3) result H4K16ac, H4K16ac levels are unchanged iPSCs variants. Regardless, altered targets upon their differentiation early germ layers. Our study defines MSL2-related disorder distinguishable clinical features, blood episignature, distinct, MSL2-specific etiology compared complex-related disorders.

Язык: Английский

Процитировано

Biallelic variation in the choline and ethanolamine transporterFLVCR1underlies a pleiotropic disease spectrum from adult neurodegeneration to severe developmental disorders DOI

Daniel G. Calame,

Jovi Huixin Wong,

Puravi Panda

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 13, 2024

Abstract FLVCR1 encodes Feline leukemia virus subgroup C receptor 1 (FLVCR1), a solute carrier (SLC) transporter within the Major Facilitator Superfamily. is widely expressed transmembrane protein with plasma membrane and mitochondrial isoforms implicated in heme, choline, ethanolamine transport. While Flvcr1 knockout mice die utero skeletal malformations defective erythropoiesis reminiscent of Diamond-Blackfan anemia, rare biallelic pathogenic variants are linked to childhood or adult-onset neurodegeneration retina, spinal cord, peripheral nervous system. We ascertained from research clinical exome sequencing 27 individuals 20 unrelated families ultra-rare missense predicted loss-of-function (pLoF) variant alleles. characterize an expansive phenotypic spectrum ranging retinitis pigmentosa severe developmental disorders microcephaly, reduced brain volume, epilepsy, spasticity, premature death. The most severely affected individuals, including three homozygous pLoF variants, share traits anemia macrocytic congenital malformations. Pathogenic primarily lie domains reduce choline transport activity compared wild-type minimal impact on stability subcellular localization. Several disrupt splicing mini-gene assay which may contribute genotype-phenotype correlations. Taken together, these data support allele-specific gene dosage model severity reflects residual activity. This study expands our understanding Mendelian demonstrates importance neurodevelopment neuronal homeostasis.

Язык: Английский

Процитировано

Complete Genomic Assembly of Mauritian Cynomolgus Macaque Killer Ig-like Receptor and Natural Killer Group 2 Haplotypes DOI

Trent M. Prall, Julie A. Karl, Joshua M. Varghese

и другие.

The Journal of Immunology, Год журнала: 2024, Номер 212(11), С. 1754 - 1765

Опубликована: Апрель 19, 2024

Mauritian-origin cynomolgus macaques (MCMs) serve as a powerful nonhuman primate model in biomedical research due to their unique genetic homogeneity, which simplifies experimental designs. Despite extensive use, comprehensive understanding of crucial immune-regulating gene families, particularly killer Ig-like receptors (KIR) and NK group 2 (NKG2), has been hindered by the lack detailed genomic reference assemblies. In this study, we employ advanced long-read sequencing techniques completely assemble eight KIR seven NKG2 haplotypes, providing an insight into structural allelic diversity these immunoregulatory clusters. Leveraging resources, prototype strategy for genotyping using short-read, whole-exome capture data, illustrating potential cost-effective multilocus at colony scale. These results mark significant enhancement MCMs underscore feasibility broad-scale investigations.

Язык: Английский

Процитировано