Similar Datasets
Project description:Mammalian neurons express extra-long pre-mRNAs which are vulnerable to misregualtion of transcriptional elongation or processing but their regulation is still largely unknown. Here we found that RNA-binding protein PSF is specifically expressed in differentiated neuron of embryonic mouse brain and is essential for the expression of extra-long neuronal gene. HITS-CLIP indicated co-transcriptional binding of PSF to the nascent pre-mRNAs. When PSF was disrupted, pre-mRNA level of long genes was down-regulated in the middle of their transcripts toward their 3’ ends. In Pol II ChIP-Seq, decrease of the RNA polymerase II density was observed parallel to pre-mRNAs, indicating that transcriptional elongation was impaired. Loss of PSF caused massive apoptosis in embryonic mouse brains and heterozygous PSF mutant mice displayed schizophrenia-like abnormal behaviors. Gene Ontology analysis demonstrated that PSF-regulated genes have essential functions at the late developmental stage of brains. Our findings indicate that PSF is required for the neuronal development through facilitating the transcriptional elongation of extra-long neuronal genes and dysfunction of PSF could be a cause of neurodevelopmental and psychiatric disorders.
2018-05-04 | GSE96082 | GEO
Project description:Mammalian neurons express extra-long pre-mRNAs which are vulnerable to misregualtion of transcriptional elongation or processing but their regulation is still largely unknown. Here we found that RNA-binding protein PSF is specifically expressed in differentiated neuron of embryonic mouse brain and is essential for the expression of extra-long neuronal gene. HITS-CLIP indicated co-transcriptional binding of PSF to the nascent pre-mRNAs. When PSF was disrupted, pre-mRNA level of long genes was down-regulated in the middle of their transcripts toward their 3’ ends. In Pol II ChIP-Seq, decrease of the RNA polymerase II density was observed parallel to pre-mRNAs, indicating that transcriptional elongation was impaired. Loss of PSF caused massive apoptosis in embryonic mouse brains and heterozygous PSF mutant mice displayed schizophrenia-like abnormal behaviors. Gene Ontology analysis demonstrated that PSF-regulated genes have essential functions at the late developmental stage of brains. Our findings indicate that PSF is required for the neuronal development through facilitating the transcriptional elongation of extra-long neuronal genes and dysfunction of PSF could be a cause of neurodevelopmental and psychiatric disorders.
2018-05-04 | GSE96080 | GEO
Project description:Mammalian neurons express extra-long pre-mRNAs which are vulnerable to misregualtion of transcriptional elongation or processing but their regulation is still largely unknown. Here we found that RNA-binding protein PSF is specifically expressed in differentiated neuron of embryonic mouse brain and is essential for the expression of extra-long neuronal gene. HITS-CLIP indicated co-transcriptional binding of PSF to the nascent pre-mRNAs. When PSF was disrupted, pre-mRNA level of long genes was down-regulated in the middle of their transcripts toward their 3’ ends. In Pol II ChIP-Seq, decrease of the RNA polymerase II density was observed parallel to pre-mRNAs, indicating that transcriptional elongation was impaired. Loss of PSF caused massive apoptosis in embryonic mouse brains and heterozygous PSF mutant mice displayed schizophrenia-like abnormal behaviors. Gene Ontology analysis demonstrated that PSF-regulated genes have essential functions at the late developmental stage of brains. Our findings indicate that PSF is required for the neuronal development through facilitating the transcriptional elongation of extra-long neuronal genes and dysfunction of PSF could be a cause of neurodevelopmental and psychiatric disorders.
2018-05-04 | GSE96081 | GEO
Project description:Mammalian neurons express extra-long pre-mRNAs which are vulnerable to misregualtion of transcriptional elongation or processing but their regulation is still largely unknown. Here we found that RNA-binding protein PSF is specifically expressed in differentiated neuron of embryonic mouse brain and is essential for the expression of extra-long neuronal gene. HITS-CLIP indicated co-transcriptional binding of PSF to the nascent pre-mRNAs. When PSF was disrupted, pre-mRNA level of long genes was down-regulated in the middle of their transcripts toward their 3’ ends. In Pol II ChIP-Seq, decrease of the RNA polymerase II density was observed parallel to pre-mRNAs, indicating that transcriptional elongation was impaired. Loss of PSF caused massive apoptosis in embryonic mouse brains and heterozygous PSF mutant mice displayed schizophrenia-like abnormal behaviors. Gene Ontology analysis demonstrated that PSF-regulated genes have essential functions at the late developmental stage of brains. Our findings indicate that PSF is required for the neuronal development through facilitating the transcriptional elongation of extra-long neuronal genes and dysfunction of PSF could be a cause of neurodevelopmental and psychiatric disorders.
2018-05-04 | GSE60241 | GEO
Project description:Mammalian neurons express extra-long pre-mRNAs which are vulnerable to misregualtion of transcriptional elongation or processing but their regulation is still largely unknown. Here we found that RNA-binding protein PSF is specifically expressed in differentiated neuron of embryonic mouse brain and is essential for the expression of extra-long neuronal gene. HITS-CLIP indicated co-transcriptional binding of PSF to the nascent pre-mRNAs. When PSF was disrupted, pre-mRNA level of long genes was down-regulated in the middle of their transcripts toward their 3’ ends. In Pol II ChIP-Seq, decrease of the RNA polymerase II density was observed parallel to pre-mRNAs, indicating that transcriptional elongation was impaired. Loss of PSF caused massive apoptosis in embryonic mouse brains and heterozygous PSF mutant mice displayed schizophrenia-like abnormal behaviors. Gene Ontology analysis demonstrated that PSF-regulated genes have essential functions at the late developmental stage of brains. Our findings indicate that PSF is required for the neuronal development through facilitating the transcriptional elongation of extra-long neuronal genes and dysfunction of PSF could be a cause of neurodevelopmental and psychiatric disorders.
2018-05-04 | GSE60238 | GEO
Project description:The RNA-binding protein Sfpq regulates long neuronal genes in transcriptional elongation
| PRJNA257815 | ENA
Project description:Circular RNAs (circRNAs) represent an abundant and conserved entity of non-coding RNAs; however, the principles of biogenesis are currently not fully understood. Here, we identify two factors, splicing factor proline/glutamine rich (SFPQ) and non-POU domain-containing octamer-binding protein (NONO), to be enriched around circRNA loci. We observe a subclass of circRNAs, coined DALI circRNAs, with distal inverted Alu elements and long flanking introns to be highly deregulated upon SFPQ knockdown. Moreover, SFPQ depletion leads to increased intron retention with concomitant induction of cryptic splicing, premature transcription termination, and polyadenylation, particularly prevalent for long introns. Aberrant splicing in the upstream and downstream regions of circRNA producing exons are critical for shaping the circRNAome, and specifically, we identify missplicing in the immediate upstream region to be a conserved driver of circRNA biogenesis. Collectively, our data show that SFPQ plays an important role in maintaining intron integrity by ensuring accurate splicing of long introns, and disclose novel features governing Alu-independent circRNA production.
| S-EPMC7819710 | biostudies-literature
Project description:BackgroundCircular RNA (circRNA) molecules, generated through non-canonical back-splicing of exon-exon junctions, have recently been implicated in diverse biological functions including transcriptional regulation and modulation of protein interactions. CircRNAs are emerging as a key component of the complex neural transcriptome implicated in brain development. However, the specific expression patterns and functions of circRNAs in human neuronal differentiation have not been explored.ResultsUsing total RNA sequencing analysis, we identified expressed circRNAs during the differentiation of human neuroepithelial stem (NES) cells into developing neurons and discovered that many circRNAs originated from host genes associated with synaptic function. Interestingly, when assessing population data, exons giving rise to circRNAs in our dataset had a higher frequency of genetic variants. Additionally, screening for RNA-binding protein sites identified enrichment of Splicing Factor Proline and Glutamine Rich (SFPQ) motifs in increased circRNAs, several of which were reduced by SFPQ knockdown and enriched in SFPQ ribonucleoprotein complexes.ConclusionsOur study provides an in-depth characterisation of circRNAs in a human neuronal differentiation model and highlights SFPQ as both a regulator and binding partner of circRNAs elevated during neuronal maturation.
| S-EPMC10224606 | biostudies-literature
Project description:Circular RNAs (circRNAs) represent an abundant and conserved entity of non-coding RNAs, however the principles of biogenesis are currently not fully understood. To elucidate features important for circRNA production, we performed global analyses of RNA-binding proteins associating with the flanking introns of circRNAs, and we identified two factors, SFPQ and NONO, to be highly enriched with circRNAs. We observe a subclass of circRNAs, coined DALI circRNAs, with distal inverted Alu elements and long introns to be highly deregulated upon SFPQ knockdown. Moreover, SFPQ depletion leads to increased intron retention with concomitant induction of cryptic splicing prevalent for long introns causing in some cases premature transcription termination and polyadenylation. Aberrant splicing in the upstream and downstream regions of circRNA producing exons are critical for shaping the circRNAome, and specifically, we identify a conserved impact of missplicing in the immediate upstream region to drive circRNA biogenesis. Collectively, our data show that SFPQ plays an important role in maintaining intron integrity by ensuring accurate splicing of long introns, and disclose novel features governing Alu-independent circRNA production.
2020-09-09 | GSE157622 | GEO
Project description:RNA-binding proteins (RBPs) are a class of proteins known for their diverse roles in RNA biogenesis, from regulating transcriptional processes in the nucleus to facilitating translation in the cytoplasm. With higher demand for RNA metabolism in the nervous system, RBP misregulation has been linked to a wide range of neurological and neurodegenerative diseases. One of the emerging RBPs implicated in neuronal function and neurodegeneration is splicing factor proline- and glutamine-rich (SFPQ). SFPQ is a ubiquitous and abundant RBP that plays multiple regulatory roles in the nucleus such as paraspeckle formation, DNA damage repair, and various transcriptional regulation processes. An increasing number of studies have demonstrated the nuclear and also cytoplasmic roles of SFPQ in neurons, particularly in post-transcriptional regulation and RNA granule formation. Not surprisingly, the misregulation of SFPQ has been linked to pathological features shown by other neurodegenerative disease-associated RBPs such as aberrant RNA splicing, cytoplasmic mislocalization, and aggregation. In this review, we discuss recent findings on the roles of SFPQ with a particular focus on those in neuronal development and homeostasis as well as its implications in neurodegenerative diseases.
| S-EPMC7582472 | biostudies-literature