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

Ximena Corso‐Díaz,

Xulong Liang,

Kiam Preston

et al.

Published: Nov. 15, 2024

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.

Language: Английский

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

et al.

Neurogenetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 24, 2025

Language: Английский

Citations

0
Maf-family bZIP transcription factor NRL interacts with RNA-binding proteins and R-loops in retinal photoreceptors DOI Creative Commons
Ximena Corso Diaz,

Xulong Liang,

Kiam Preston

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: March 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.

Language: Английский

Citations

0
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

et al.

Growth Factors, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 11

Published: April 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.

Language: Английский

Citations

0
Bi-allelic UGGT1 variants cause a congenital disorder of glycosylation DOI Creative Commons
Zain Dardas,

Laura Harrold,

Daniel G. Calame

et al.

The American Journal of Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
A longitudinal analysis of function annotations of the human proteome reveals consistently high biases DOI Creative Commons
An Phan, Parnal Joshi, Claus Kadelka

et al.

Database, Journal Year: 2025, Volume and Issue: 2025

Published: Jan. 1, 2025

Abstract 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

Language: Английский

Citations

0
DDX3X syndrome: From clinical phenotypes to biological insights DOI

Alexa von Mueffling,

Marta García-Forn, Silvia De Rubeis

et al.

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: July 8, 2024

Abstract DDX3X syndrome is a neurodevelopmental disorder accounting for up to 3% of cases intellectual disability (ID) and affecting primarily females. Individuals diagnosed with can also present behavioral challenges, motor delays movement disorders, epilepsy, congenital malformations. caused by mutations in the X‐linked gene , which encodes DEAD‐box RNA helicase critical roles metabolism, including mRNA translation. Emerging discoveries from animal models are unveiling fundamental role neuronal differentiation development, especially neocortex. Here, we review current knowledge genetic neurobiological mechanisms underlying their relationship clinical phenotypes. image

Language: Английский

Citations

2
Biallelic variation in the choline and ethanolamine transporterFLVCR1underlies a pleiotropic disease spectrum from adult neurodegeneration to severe developmental disorders DOI Creative Commons
Daniel G. Calame,

Jovi Huixin Wong,

Puravi Panda

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

Citations

1
Drosophila melanogaster MLE Helicase Functions Beyond Dosage Compensation: Molecular Nature and Pleiotropic Effect of mle[9] Mutation DOI
German A. Ashniev, С. Г. Георгиева, J. V. Nikolenko

et al.

Russian Journal of Genetics, Journal Year: 2024, Volume and Issue: 60(4), P. 460 - 470

Published: April 1, 2024

Language: Английский

Citations

1
MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature DOI Creative Commons
Remzi Karayol,

Maria Carla Borroto,

Sadegheh Haghshenas

et al.

The American Journal of Human Genetics, Journal Year: 2024, Volume and Issue: 111(7), P. 1330 - 1351

Published: May 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.

Language: Английский

Citations

1
The role of DEAD- and DExH-box RNA helicases in neurodevelopmental disorders DOI Creative Commons

Johannes Lederbauer,

Sarada Das, Amélie Piton

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Aug. 1, 2024

Neurodevelopmental disorders (NDDs) represent a large group of with an onset in the neonatal or early childhood period; NDDs include intellectual disability (ID), autism spectrum (ASD), attention deficit hyperactivity (ADHD), seizures, various motor disabilities and abnormal muscle tone. Among many underlying Mendelian genetic causes for these conditions, genes coding proteins involved all aspects gene expression pathway, ranging from transcription, splicing, translation to eventual RNA decay, feature rather prominently. Here we focus on two families helicases (DEAD- DExH-box helicases). Genetic variants several have recently been shown be associated NDD. We address constraints helicases, types pathological which discovered discuss biological pathways affected helicase are involved.

Language: Английский

Citations

1