Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NSUN7 is an RNA:m5C catalytically inactive protein that regulates sperm flagellum assembly [scRNA-seq]

ABSTRACT: Defects in Nsun7, a member of the main RNA:m5C modifying enzymes, known as the NOL1/NOP2/Sun domain (NSUN) family, cause male infertility. The NSUN family includes NSUN1-7, all possessing conserved motifs IV and VI essential for RNA:m5C formation. However, due to the controversy regarding the catalytic activity and RNA substrates of NSUN7, the pathogenic mechanism underlyingof NSUN7-related male infertility remains unclear. Here, we showed that NSUN7 is predominantly enriched in adult mouse testes, particularly in elongated spermatids. Through m5C mass spectrometry detection and bisulfite sequencing, we found that knockout of Nsun7 has no impact on testicular RNA:m5C modification. Mechanistically, NSUN7 loses its ability to bind S-adenosylmethionine (SAM) due to sequence variations in motif IV compared towith the conserved residues observed in NSUN1-6. Notably, the key SAM-binding Asp in motif IV is replaced by Leu in NSUN7, thereby abolishing SAM binding. Nsun7 deficiency impairs sperm progressive motility, accompanied by defects in axonemes and mispositioning of longitudinal columns. Single-cell RNA sequencing showed that knockout of Nsun7 results in a significantly decrease in the levels of a cohort of mRNAs related to cilium organization in elongated spermatids. Collectively, our study demonstrateds that NSUN7 is the only RNA:m5C catalytically inactive member in the NSUN family, and that it regulates sperm flagellum assembly by modulating the expression of cilium organization-associated genes.

ORGANISM(S): Mus musculus

PROVIDER: GSE297919 | GEO | 2025/11/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

NSUN7 is an RNA:m5C catalytically inactive protein that regulates sperm flagellum assembly

Project description:Defects in Nsun7, a member of the main RNA:m5C modifying enzymes, known as the NOL1/NOP2/Sun domain (NSUN) family, cause male infertility. The NSUN family includes NSUN1-7, all possessing conserved motifs IV and VI essential for RNA:m5C formation. However, due to the controversy regarding the catalytic activity and RNA substrates of NSUN7, the pathogenic mechanism underlyingof NSUN7-related male infertility remains unclear. Here, we showed that NSUN7 is predominantly enriched in adult mouse testes, particularly in elongated spermatids. Through m5C mass spectrometry detection and bisulfite sequencing, we found that knockout of Nsun7 has no impact on testicular RNA:m5C modification. Mechanistically, NSUN7 loses its ability to bind S-adenosylmethionine (SAM) due to sequence variations in motif IV compared towith the conserved residues observed in NSUN1-6. Notably, the key SAM-binding Asp in motif IV is replaced by Leu in NSUN7, thereby abolishing SAM binding. Nsun7 deficiency impairs sperm progressive motility, accompanied by defects in axonemes and mispositioning of longitudinal columns. Single-cell RNA sequencing showed that knockout of Nsun7 results in a significantly decrease in the levels of a cohort of mRNAs related to cilium organization in elongated spermatids. Collectively, our study demonstrateds that NSUN7 is the only RNA:m5C catalytically inactive member in the NSUN family, and that it regulates sperm flagellum assembly by modulating the expression of cilium organization-associated genes.

2025-11-12 | GSE297485 | GEO

Positioning of sperm tail longitudinal columns depend on Nsun7, an RNA binding protein destabilizing elongated spermatid transcripts (BS-RNA-Seq)

Project description:Spermatozoid’s flagella assemble in transcriptionally silent spermatids and thus depends on post-transcriptional regulation of gene expression. Mutations in Nsun7 gene are known to cause male infertility in human and mice. We identified m5C-specific Nsun7 RNA methyltransferase as a protein present in elongated spermatids and interacting with RNAs specific for this type of spermatozoid’s precursor cells. Inactivation of Nsun7 gene in mice leads to upregulation of its RNA interactors, thus indicating that Nsun7 downregulates a set of RNAs in the elongated spermatids. A physiologic consequence of Nsun7 gene knockout is male infertility, which is mechanistically explained by the observed mispositioning of longitudinal columns relative to the axonemal microtubular doublets leading to motility defect.

2025-04-23 | GSE281866 | GEO

Positioning of sperm tail longitudinal columns depend on Nsun7, an RNA binding protein destabilizing elongated spermatid transcripts (RNA-Seq)

2025-04-23 | GSE281586 | GEO

Positioning of sperm tail longitudinal columns depend on Nsun7, an RNA binding protein destabilizing elongated spermatid transcripts (CLIP-Seq)

2025-04-23 | GSE281899 | GEO

Genome-wide miCLIP-Seq reveals methylation targets and RNA interactome of human NOP2/NSUN1

Project description:5-Methylcytosine (m5C) is a base modification broadly found on a variety on coding and non-coding RNAs in the human transcriptome. In eukaryotes m5C is catalyzed by enzymes of the NOL1/NOP2/SUN domain (NSUN) family, which is composed of seven members in humans (NSUN1-7). NOP2/NSUN1, a member of this family, has been mostly characterized in budding yeast as an essential ribosome biogenesis factor required for the deposition of m5C at position C2870 of the 25S rRNA. Although human NOP2/NSUN1 has been known to be an oncogene overexpressed in several types of cancer for decades, its functions remain poorly characterized. To better define the roles of NOP2/NSUN1 in human cells, we used an adapted genome-wide methylation of individual-nucleotide-resolution crosslinking and immunoprecipitation-sequencing (miCLIP-seq) approach to identify its RNA methylation targets. Our analysis revealed that vault RNA 1.2 (vtRNA1.2) and 28S rRNA are NOP2/NSUN1-specific methylated targets. In addition, NOP2/NSUN1 predominantly binds to rRNA, followed by C/D box snoRNA, and other ncRNAs. Together, our data provided a genome-wide spectrum of NOP2/NSUN1 binding RNA and methylated target RNA for understanding the function of human NOP2/NSUN1.

2021-11-15 | GSE188735 | GEO

Proteome of wild type and Nsun7 knockout mice testis

Project description:Investigation of a new RNA-modification-based mechanism in mammalian spermatogenesis. We created a mice line devoid of testis-specific m5C RNA methyltransferase Nsun7. These mice demonstrated male infertility due to a peculiar defect in sperm tail assembly – mispositioning of the longitudinal columns of the fibrous sheath. The whole testis proteomes of wild type and Nsun7 knockout mice were obtained to study the molecular pathways affected by NSUN7.

2025-03-07 | PXD057007 | Pride

NSUN1-m5C is linked to TDP-43 neurotoxicity

Project description:In amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the nuclear RNA-binding protein TDP-43 mislocalises to the cytoplasm and forms insoluble aggregates, but the mechanisms controlling this remain unclear. We define a native TDP-43 interactome in human SH-SY5Y cells and identify proteins linked to the 5-methylcytosine (m5C) RNA modification as highly enriched. Using a Drosophila model of TDP-43 pathology, we show that aberrant activity of m5C-RNA methyltransferases Nsun1 drives TDP-43-induced m5C-RNA hypermethylation, while Nsun1 downregulation alleviates TDP-43–induced degeneration, lifespan deficits, and cytoplasmic accumulation. In human cells, TDP-43 selectively interacts with NSUN1 isoform 3 independently of RNA. Furthermore, NSUN1 is nucleolar and TDP-43 is largely nucleoplasmic, yet they interact in both compartments, suggesting functional roles beyond their predominant localisations. In ALS/FTD post-mortem frontal cortex, NSUN1 isoform 3 persists, while the shorter isoform is reduced, suggesting that a pool of NSUN1 capable of contributing to pathological TDP-43 interactions remains in disease. These findings suggest that TDP-43 neurotoxicity is coupled to NSUN1 activation and m5C-RNA methylation, revealing a potential therapeutic axis in ALS/FTD.

2025-11-03 | PXD070093 | Pride

Small non-coding RNA expression in mouse elongated spermatids

Project description:In order to discover novel small RNAs expressed in elongated spermatids, we isolated elongated spermatids from mouse testis. The small RNA fraction (18-40nt) was cloned and sequenced from total RNA. RNAs extracted from elongated spermatids were used for high throughput sequencing analysis

2013-01-31 | E-GEOD-40397 | biostudies-arrayexpress

TMT-based proteomics analysis of mouse germ cells

Project description:The proteome changes were quantified in RibosomeRPL39L-/- spermatocytes and elongated spermatids using TMT 6-plex, and in spermatogonia, spermatocytes, round spermatids and elongated spermatids using TMT 10-plex by LC-MS/MS.

2022-10-05 | PXD020874 | Pride

Small non-coding RNA expression in mouse elongated spermatids

2013-01-31 | GSE40397 | GEO