Nopp140-chaperoned 2’-O-methylation of small nuclear RNAs in Cajal bodies ensures splicing fidelity
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE173171 | GEO | 2021/07/01
REPOSITORIES: GEO
Similar Datasets
Project description:The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. We examined the non-random positioning of Cajal bodies (CBs), major NBs involved in spliceosomal snRNP assembly, and their role in genome organization. CBs are predominantly located at the periphery of chromosome territories at a multi-chromosome interface. Genome-wide chromatin conformation capture analysis (4C-seq) using CB-interacting loci revealed that CB-associated regions are enriched with highly expressed histone genes and U small nuclear and nucleoar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. We observed a number of CB-dependent gene positioning events on chromosome 1. RNAi-mediated disassembly of CBs disrupts the CB-targeting gene clusters and suppresses the expression of U sn/snoRNA and histone genes. This loss of spliceosomal snRNP production resulted in increased splicing noise, even in CB-distal regions. We conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.
2016-03-21 | GSE77915 | GEO
Project description:The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. We examined the non-random positioning of Cajal bodies (CBs), major NBs involved in spliceosomal snRNP assembly, and their role in genome organization. CBs are predominantly located at the periphery of chromosome territories at a multi-chromosome interface. Genome-wide chromatin conformation capture analysis (4C-seq) using CB-interacting loci revealed that CB-associated regions are enriched with highly expressed histone genes and U small nuclear and nucleoar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. We observed a number of CB-dependent gene positioning events on chromosome 1. RNAi-mediated disassembly of CBs disrupts the CB-targeting gene clusters and suppresses the expression of U sn/snoRNA and histone genes. This loss of spliceosomal snRNP production resulted in increased splicing noise, even in CB-distal regions. We conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.
2016-03-21 | GSE77914 | GEO
Project description:The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. We examined the non-random positioning of Cajal bodies (CBs), major NBs involved in spliceosomal snRNP assembly, and their role in genome organization. CBs are predominantly located at the periphery of chromosome territories at a multi-chromosome interface. Genome-wide chromatin conformation capture analysis (4C-seq) using CB-interacting loci revealed that CB-associated regions are enriched with highly expressed histone genes and U small nuclear and nucleoar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. We observed a number of CB-dependent gene positioning events on chromosome 1. RNAi-mediated disassembly of CBs disrupts the CB-targeting gene clusters and suppresses the expression of U sn/snoRNA and histone genes. This loss of spliceosomal snRNP production resulted in increased splicing noise, even in CB-distal regions. We conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.
2016-03-21 | GSE77913 | GEO
Project description:Targeted cancer therapy for squamous cell carcinoma (SCC) has made little progress largely due to a lack of knowledge of the driving genomic alterations. Small non-coding RNAs (sncRNAs) as a potential biomarker and therapeutic target to SCC remain a challenge. We analyzed sncRNAs microarray in 108 fresh frozen specimens of esophageal squamous cell carcinoma (ESCC) as discovery set and assessed associations between sncRNAs and recurrence-free survival. SncRNA signature identified was externally validated in two independent cohorts. We investigated the functional consequences of sncRNA identified and its integrative analysis of complex cancer genomics. We identified 3 recurrence-associated sncRNAs (miR-223, miR-1269a and nc886) from discovery set and proved risk prediction model externally in high and low volume centers. We uncovered through in vitro experiment that nc886 was down-regulated by hypermethylation of its promoter region and influences splicing of pre-mRNAs with minor introns by regulating expression of minor spliceosomal small nuclear RNAs (snRNAs) such as RNU4atac. Integrative analysis from lung SCC data in The Cancer Genome Atlas revealed that patients with lower expression of nc886 had more genetic alterations of TP53, DNA damage response and cell cycle genes. nc886 inhibits minor splicing to suppress expression of certain oncogenes such as PARP1 and E2F family containing minor introns. We present risk prediction model with sncRNAs for ESCC. Among them, nc886 may contribute to complete minor splicing via regulation of minor spliceosomal snRNAs supporting the notion that aberrant alteration in minor splicing might be a key driver of ESCC. Clinical study ESCC tumor samples vs. ESCC normal samples
2016-06-30 | E-GEOD-55856 | biostudies-arrayexpress
Project description:Targeted cancer therapy for squamous cell carcinoma (SCC) has made little progress largely due to a lack of knowledge of the driving genomic alterations. Small non-coding RNAs (sncRNAs) as a potential biomarker and therapeutic target to SCC remain a challenge. We analyzed sncRNAs microarray in 108 fresh frozen specimens of esophageal squamous cell carcinoma (ESCC) as discovery set and assessed associations between sncRNAs and recurrence-free survival. SncRNA signature identified was externally validated in two independent cohorts. We investigated the functional consequences of sncRNA identified and its integrative analysis of complex cancer genomics. We identified 3 recurrence-associated sncRNAs (miR-223, miR-1269a and nc886) from discovery set and proved risk prediction model externally in high and low volume centers. We uncovered through in vitro experiment that nc886 was down-regulated by hypermethylation of its promoter region and influences splicing of pre-mRNAs with minor introns by regulating expression of minor spliceosomal small nuclear RNAs (snRNAs) such as RNU4atac. Integrative analysis from lung SCC data in The Cancer Genome Atlas revealed that patients with lower expression of nc886 had more genetic alterations of TP53, DNA damage response and cell cycle genes. nc886 inhibits minor splicing to suppress expression of certain oncogenes such as PARP1 and E2F family containing minor introns. We present risk prediction model with sncRNAs for ESCC. Among them, nc886 may contribute to complete minor splicing via regulation of minor spliceosomal snRNAs supporting the notion that aberrant alteration in minor splicing might be a key driver of ESCC. Clinical study ESCC tumor samples.
2016-06-30 | E-GEOD-66258 | biostudies-arrayexpress
Project description:Targeted cancer therapy for squamous cell carcinoma (SCC) has made little progress largely due to a lack of knowledge of the driving genomic alterations. Small non-coding RNAs (sncRNAs) as a potential biomarker and therapeutic target to SCC remain a challenge. We analyzed sncRNAs microarray in 108 fresh frozen specimens of esophageal squamous cell carcinoma (ESCC) as discovery set and assessed associations between sncRNAs and recurrence-free survival. SncRNA signature identified was externally validated in two independent cohorts. We investigated the functional consequences of sncRNA identified and its integrative analysis of complex cancer genomics. We identified 3 recurrence-associated sncRNAs (miR-223, miR-1269a and nc886) from discovery set and proved risk prediction model externally in high and low volume centers. We uncovered through in vitro experiment that nc886 was down-regulated by hypermethylation of its promoter region and influences splicing of pre-mRNAs with minor introns by regulating expression of minor spliceosomal small nuclear RNAs (snRNAs) such as RNU4atac. Integrative analysis from lung SCC data in The Cancer Genome Atlas revealed that patients with lower expression of nc886 had more genetic alterations of TP53, DNA damage response and cell cycle genes. nc886 inhibits minor splicing to suppress expression of certain oncogenes such as PARP1 and E2F family containing minor introns. We present risk prediction model with sncRNAs for ESCC. Among them, nc886 may contribute to complete minor splicing via regulation of minor spliceosomal snRNAs supporting the notion that aberrant alteration in minor splicing might be a key driver of ESCC. Pre-clinical study Analysis of Esophageal Squamous Cell Carcinoma cell lines knocked-down for nc886 and vault RNA VTRNA1-1 via antisense oligonucleotide (ASO)-targeting.
2016-06-30 | E-GEOD-55854 | biostudies-arrayexpress
Project description:Substoichiometric ribose methylations in spliceosomal snRNAs
| PRJNA414213 | ENA
Project description:RNA splicing and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using an in vivo biotinylation tagging approach in mice we show that XAB2, the human homologue of the yeast pre-mRNA-splicing factor SYF1 has a functional role in Nucleotide Excision Repair (NER) and the DNA damage response (DDR) in mammals. XAB2 interacts with spliceosome factors and is part of the core spliceosome that binds to spliceosomal U4 and U6 snRNAs during hepatic development. Ablation of XAB2 leads to defective NER, intron retention, the aberrant accumulation of pre-mRNAs and to a faulty ATM/ATR DDR signaling. Using functional approaches, we find that XAB2 dissociates from RNA targets upon persistent DNA damage or transcription blockage and from spliceosomal RNAs in the NER-defective developing livers. Thus, XAB2 functionally links NER to the spliceosomal response to DNA damage during hepatic development with important ramifications for transcription-coupled DNA repair disorders.
2021-09-08 | PXD014084 | Pride
Project description:Targeted cancer therapy for squamous cell carcinoma (SCC) has made little progress largely due to a lack of knowledge of the driving genomic alterations. Small non-coding RNAs (sncRNAs) as a potential biomarker and therapeutic target to SCC remain a challenge. We analyzed sncRNAs microarray in 108 fresh frozen specimens of esophageal squamous cell carcinoma (ESCC) as discovery set and assessed associations between sncRNAs and recurrence-free survival. SncRNA signature identified was externally validated in two independent cohorts. We investigated the functional consequences of sncRNA identified and its integrative analysis of complex cancer genomics. We identified 3 recurrence-associated sncRNAs (miR-223, miR-1269a and nc886) from discovery set and proved risk prediction model externally in high and low volume centers. We uncovered through in vitro experiment that nc886 was down-regulated by hypermethylation of its promoter region and influences splicing of pre-mRNAs with minor introns by regulating expression of minor spliceosomal small nuclear RNAs (snRNAs) such as RNU4atac. Integrative analysis from lung SCC data in The Cancer Genome Atlas revealed that patients with lower expression of nc886 had more genetic alterations of TP53, DNA damage response and cell cycle genes. nc886 inhibits minor splicing to suppress expression of certain oncogenes such as PARP1 and E2F family containing minor introns. We present risk prediction model with sncRNAs for ESCC. Among them, nc886 may contribute to complete minor splicing via regulation of minor spliceosomal snRNAs supporting the notion that aberrant alteration in minor splicing might be a key driver of ESCC.
2016-06-30 | GSE55856 | GEO
Project description:Targeted cancer therapy for squamous cell carcinoma (SCC) has made little progress largely due to a lack of knowledge of the driving genomic alterations. Small non-coding RNAs (sncRNAs) as a potential biomarker and therapeutic target to SCC remain a challenge. We analyzed sncRNAs microarray in 108 fresh frozen specimens of esophageal squamous cell carcinoma (ESCC) as discovery set and assessed associations between sncRNAs and recurrence-free survival. SncRNA signature identified was externally validated in two independent cohorts. We investigated the functional consequences of sncRNA identified and its integrative analysis of complex cancer genomics. We identified 3 recurrence-associated sncRNAs (miR-223, miR-1269a and nc886) from discovery set and proved risk prediction model externally in high and low volume centers. We uncovered through in vitro experiment that nc886 was down-regulated by hypermethylation of its promoter region and influences splicing of pre-mRNAs with minor introns by regulating expression of minor spliceosomal small nuclear RNAs (snRNAs) such as RNU4atac. Integrative analysis from lung SCC data in The Cancer Genome Atlas revealed that patients with lower expression of nc886 had more genetic alterations of TP53, DNA damage response and cell cycle genes. nc886 inhibits minor splicing to suppress expression of certain oncogenes such as PARP1 and E2F family containing minor introns. We present risk prediction model with sncRNAs for ESCC. Among them, nc886 may contribute to complete minor splicing via regulation of minor spliceosomal snRNAs supporting the notion that aberrant alteration in minor splicing might be a key driver of ESCC.
2016-06-30 | GSE55854 | GEO