Browse
Submit Data
Databases
API
Help

Dataset Information

50 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

FOXP3 interacts with hnRNPF to modulate pre-mRNA alternative splicing.

ABSTRACT: FOXP3 promotes the development and function of regulatory T cells mainly through regulating the transcription of target genes. RNA alternative splicing has been implicated in a wide range of physiological and pathophysiological processes. We report here that FOXP3 associates with heterogeneous nuclear ribonucleoprotein (hnRNP) F through the exon 2-encoded region of FOXP3 and the second quasi-RNA recognition motif (qRRM) of hnRNPF. FOXP3 represses the ability of hnRNPF to bind to its target pre-mRNA and thus modulates RNA alternative splicing. Furthermore, overexpression of mouse hnRNPF in in vitro-differentiated regulatory T cells (Tregs) reduced their suppressive function. Thus, our studies identify a novel mechanism by which FOXP3 regulates mRNA alternative splicing to modulate the function of regulatory T cells.

SUBMITTER: Du J

PROVIDER: S-EPMC6028976 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

FOXP3 interacts with hnRNPF to modulate pre-mRNA alternative splicing.

Du Jianguang J Wang Qun Q Ziegler Steven F SF Zhou Baohua B

The Journal of biological chemistry 20180517 26

FOXP3 promotes the development and function of regulatory T cells mainly through regulating the transcription of target genes. RNA alternative splicing has been implicated in a wide range of physiological and pathophysiological processes. We report here that FOXP3 associates with heterogeneous nuclear ribonucleoprotein (hnRNP) F through the exon 2-encoded region of FOXP3 and the second quasi-RNA recognition motif (qRRM) of hnRNPF. FOXP3 represses the ability of hnRNPF to bind to its target pre-m ...[more]

PMID: 29773655

Similar Datasets

Alternative pre-mRNA splicing switches modulate gene expression in late erythropoiesis.

Project description:Differentiating erythroid cells execute a unique gene expression program that insures synthesis of the appropriate proteome at each stage of maturation. Standard expression microarrays provide important insight into erythroid gene expression but cannot detect qualitative changes in transcript structure, mediated by RNA processing, that alter structure and function of encoded proteins. We analyzed stage-specific changes in the late erythroid transcriptome via use of high-resolution microarrays that detect altered expression of individual exons. Ten differentiation-associated changes in erythroblast splicing patterns were identified, including the previously known activation of protein 4.1R exon 16 splicing. Six new alternative splicing switches involving enhanced inclusion of internal cassette exons were discovered, as well as 3 changes in use of alternative first exons. All of these erythroid stage-specific splicing events represent activated inclusion of authentic annotated exons, suggesting they represent an active regulatory process rather than a general loss of splicing fidelity. The observation that 3 of the regulated transcripts encode RNA binding proteins (SNRP70, HNRPLL, MBNL2) may indicate significant changes in the RNA processing machinery of late erythroblasts. Together, these results support the existence of a regulated alternative pre-mRNA splicing program that is critical for late erythroid differentiation.

| S-EPMC2665901 | biostudies-literature

Prediction of alternative pre-mRNA splicing outcomes.

Project description:To understand the biological impact of alternative pre-mRNA splicing, it is vital to know which exons are involved, what protein domains they encode, and how the translated isoforms differ. Therefore, we developed a computational pipeline (RiboSplitter) focused on functional effect prediction. It builds on event-based alternative splicing detection with additional filtering steps leading to more efficient statistical testing, and with detection of isoform-specific protein changes. A key methodological advance is reading frame prediction by translating exonic DNA in all possible frames, then finding a single open reading frame, or a single frame with matches to known proteins of the gene. This allowed unambiguous translation in 93.9% of alternative splicing events when tested on RNA-sequencing data of B cells from Sjögren's syndrome patients. RiboSplitter does not depend on reference annotations and translates events even when one or both isoform(s) are novel (unannotated). RiboSplitter's visualizations illustrate each event with translation outcomes, show event location within the gene, and align exons to protein domains.

| S-EPMC10651857 | biostudies-literature

Mechanisms and Regulation of Alternative Pre-mRNA Splicing.

Project description:Precursor messenger RNA (pre-mRNA) splicing is a critical step in the posttranscriptional regulation of gene expression, providing significant expansion of the functional proteome of eukaryotic organisms with limited gene numbers. Split eukaryotic genes contain intervening sequences or introns disrupting protein-coding exons, and intron removal occurs by repeated assembly of a large and highly dynamic ribonucleoprotein complex termed the spliceosome, which is composed of five small nuclear ribonucleoprotein particles, U1, U2, U4/U6, and U5. Biochemical studies over the past 10 years have allowed the isolation as well as compositional, functional, and structural analysis of splicing complexes at distinct stages along the spliceosome cycle. The average human gene contains eight exons and seven introns, producing an average of three or more alternatively spliced mRNA isoforms. Recent high-throughput sequencing studies indicate that 100% of human genes produce at least two alternative mRNA isoforms. Mechanisms of alternative splicing include RNA-protein interactions of splicing factors with regulatory sites termed silencers or enhancers, RNA-RNA base-pairing interactions, or chromatin-based effects that can change or determine splicing patterns. Disease-causing mutations can often occur in splice sites near intron borders or in exonic or intronic RNA regulatory silencer or enhancer elements, as well as in genes that encode splicing factors. Together, these studies provide mechanistic insights into how spliceosome assembly, dynamics, and catalysis occur; how alternative splicing is regulated and evolves; and how splicing can be disrupted by cis- and trans-acting mutations leading to disease states. These findings make the spliceosome an attractive new target for small-molecule, antisense, and genome-editing therapeutic interventions.

| S-EPMC4526142 | biostudies-literature

Control of alternative pre-mRNA splicing by Ca(++) signals.

Project description:Alternative pre-mRNA splicing is a common way of gene expression regulation in metazoans. The selective use of specific exons can be modulated in response to various manipulations that alter Ca(++) signals, particularly in neurons. A number of splicing factors have also been found to be controlled by Ca(++) signals. Moreover, pre-mRNA elements have been identified that are essential and sufficient to mediate Ca(++)-regulated splicing, providing model systems for dissecting the involved molecular components. In neurons, this regulation likely contributes to the fine-tuning of neuronal properties.

| S-EPMC3500379 | biostudies-literature

U1-independent pre-mRNA splicing contributes to the regulation of alternative splicing.

Project description:U1 snRNP plays a crucial role in the 5' splice site recognition during splicing. Here we report the first example of naturally occurring U1-independent U2-type splicing in humans. The U1 components were not included in the pre-spliceosomal E complex formed on the human F1gamma (hF1gamma) intron 9 in vitro. Moreover, hF1gamma intron 9 was efficiently spliced even in U1-disrupted Xenopus oocytes as well as in U1-inactivated HeLa nuclear extracts. Finally, hF1gamma exon 9 skipping induced by an alternative splicing regulator Fox-1 was impaired when intron 9 was changed to the U1-dependent one. Our results suggest that U1-independent splicing contributes to the regulation of alternative splicing of a class of pre-mRNAs.

| S-EPMC2665233 | biostudies-literature

SOX2 interacts with hnRNPK to modulate alternative splicing in mouse embryonic stem cells.

Project description:BackgroundSOX2 is a determinant transcription factor that governs the balance between stemness and differentiation by influencing transcription and splicing programs. The role of SOX2 is intricately shaped by its interactions with specific partners. In the interactome of SOX2 in mouse embryonic stem cells (mESCs), there is a cohort of heterogeneous nuclear ribonucleoproteins (hnRNPs) that contributes to multiple facets of gene expression regulation. However, the cross-talk between hnRNPs and SOX2 in gene expression regulation remains unclear.ResultsHere we demonstrate the indispensable role of the co-existence of SOX2 and heterogeneous nuclear ribonucleoprotein K (hnRNPK) in the maintenance of pluripotency in mESCs. While hnRNPK directly interacts with the SOX2-HMG DNA-binding domain and induces the collapse of the transcriptional repressor 7SK small nuclear ribonucleoprotein (7SK snRNP), hnRNPK does not influence SOX2-mediated transcription, either by modulating the interaction between SOX2 and its target cis-regulatory elements or by facilitating transcription elongation as indicated by the RNA-seq analysis. Notably, hnRNPK enhances the interaction of SOX2 with target pre-mRNAs and collaborates with SOX2 in regulating the alternative splicing of a subset of pluripotency genes.ConclusionsThese data reveal that SOX2 and hnRNPK have a direct protein-protein interaction, and shed light on the molecular mechanisms by which hnRNPK collaborates with SOX2 in alternative splicing in mESCs.

| S-EPMC11331657 | biostudies-literature

Genetic variation of pre-mRNA alternative splicing in human populations.

Project description:The precise splicing outcome of a transcribed gene is controlled by complex interactions between cis regulatory splicing signals and trans-acting regulators. In higher eukaryotes, alternative splicing is a prevalent mechanism for generating transcriptome and proteome diversity. Alternative splicing can modulate gene function, affect organismal phenotype and cause disease. Common genetic variation that affects splicing regulation can lead to differences in alternative splicing between human individuals and consequently impact expression level or protein function. In several well-documented examples, such natural variation of alternative splicing has indeed been shown to influence disease susceptibility and drug response. With new microarray and sequencing-based genomic technologies that can analyze eukaryotic transcriptomes at the exon or nucleotide level, it has become possible to globally compare the alternative splicing profiles across human individuals in any tissue or cell type of interest. Recent large-scale transcriptome studies using high-density splicing-sensitive microarray and deep RNA sequencing (RNA-Seq) have revealed widespread genetic variation of alternative splicing in humans. In the future, an extensive catalog of alternative splicing variation in human populations will help elucidate the molecular underpinnings of complex traits and human diseases, and shed light on the mechanisms of splicing regulation in human cells.

| S-EPMC3339278 | biostudies-literature

Inflammation-Induced Alternative Pre-mRNA Splicing in Mouse Alveolar Macrophages.

Project description:Alveolar macrophages serve as central orchestrators of inflammatory responses in the lungs, both initiating their onset and promoting their resolution. However, the mechanisms that program macrophages for these dynamic responses are not fully understood. Over 95% of all mammalian genes undergo alternative pre-mRNA splicing. While alternative splicing has been shown to regulate inflammatory responses in macrophages in vitro, it has not been investigated on a genome-wide scale in vivo Here we used RNAseq to investigate alternative pre-mRNA splicing in alveolar macrophages isolated from lipopolysaccharide (LPS)-treated mice during the peak of inflammation and during its resolution. We found that lung inflammation induced substantial alternative pre-mRNA splicing in alveolar macrophages. The number of changes in isoform usage was greatest at the peak of inflammation and involved multiple classes of alternative pre-mRNA splicing events. Comparative pathway analysis of inflammation-induced changes in alternative pre-mRNA splicing and differential gene expression revealed overlap of pathways enriched for immune responses such as chemokine signaling and cellular metabolism. Moreover, alternative pre-mRNA splicing of genes in metabolic pathways differed in tissue resident vs. recruited (blood monocyte-derived) alveolar macrophages and corresponded to changes in core metabolism, including a switch to Warburg-like metabolism in recruited macrophages with increased glycolysis and decreased flux through the tricarboxylic acid cycle.

| S-EPMC7003074 | biostudies-literature

The Function of Pre-mRNA Alternative Splicing in Mammal Spermatogenesis.

Project description:Alternative pre-mRNA splicing plays important roles in co-transcriptional and post-transcriptional regulation of gene expression functioned during many developmental processes, such as spermatogenesis. The studies focusing on alternative splicing on spermatogenesis supported the notion that the development of testis is regulated by a higher level of alternative splicing than other tissues. Here, we aim to review the mechanisms underlying alternative splicing, particularly the splicing variants functioned in the process of spermatogenesis and the male infertility. There are five points regarding the alternative splicing including ⅰ) a brief introduction of alternative pre-mRNA splicing; ⅱ) the alternative splicing events in spermatogenesis-associated genes enriched in different stages of spermatogenesis; ⅲ) the mechanisms of alternative splicing regulation, such as splicing factors and m6A demethylation; ⅳ) the splice site recognition and alternative splicing, including the production and degradation of abnormal transcripts caused by gene variations and nonsense-mediated mRNA decay, respectively; ⅴ) abnormal alternative splicing correlated with male infertility. Taking together, this review highlights the impacts of alternative splicing and splicing variants in mammal spermatogenesis and provides new insights of the potential application of the alternative splicing into the therapy of male infertility.

| S-EPMC6930371 | biostudies-literature

RNA G-quadruplex secondary structure promotes alternative splicing via the RNA-binding protein hnRNPF.

Project description:It is generally thought that splicing factors regulate alternative splicing through binding to RNA consensus sequences. In addition to these linear motifs, RNA secondary structure is emerging as an important layer in splicing regulation. Here we demonstrate that RNA elements with G-quadruplex-forming capacity promote exon inclusion. Destroying G-quadruplex-forming capacity while keeping G tracts intact abrogates exon inclusion. Analysis of RNA-binding protein footprints revealed that G quadruplexes are enriched in heterogeneous nuclear ribonucleoprotein F (hnRNPF)-binding sites and near hnRNPF-regulated alternatively spliced exons in the human transcriptome. Moreover, hnRNPF regulates an epithelial-mesenchymal transition (EMT)-associated CD44 isoform switch in a G-quadruplex-dependent manner, which results in inhibition of EMT. Mining breast cancer TCGA (The Cancer Genome Atlas) data sets, we demonstrate that hnRNPF negatively correlates with an EMT gene signature and positively correlates with patient survival. These data suggest a critical role for RNA G quadruplexes in regulating alternative splicing. Modulation of G-quadruplex structural integrity may control cellular processes important for tumor progression.

| S-EPMC5769772 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data