AKAP95 regulates splicing through scaffolding RNAs and RNA processing factors
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE81916
PROVIDER: PRJNA323422 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Alternative splicing of pre-mRNAs significantly contributes to the complexity of gene expression in higher organisms, but the regulation of the splice site selection remains incompletely understood. We have previously demonstrated that a chromatin-associated protein, AKAP95 (AKAP8), has a remarkable activity in enhancing chromatin transcription. In this study, we have shown that AKAP95 physically interacts with many factors involved in transcription and RNA processing, and functionally regulates pre-mRNA splicing. AKAP95 directly promotes splicing in vitro and the inclusion of a specific exon of an endogenous gene FAM126A. The N-terminal YG-rich domain of AKAP95 is important for its binding to RNA processing factors including selective groups of hnRNP proteins, and its zinc finger domains are critical for pre-mRNA binding. Genome-wide binding assays revealed that AKAP95 bound preferentially to proximal intronic regions on a large number of pre-mRNAs in human transcriptome, and AKAP95 depletion predominantly resulted in reduced inclusion of many exons. AKAP95 also selectively coordinates with hnRNP H/F and U proteins in regulating alternative splicing events. We have further shown that AKAP95 directly interacts with itself. Taken together, our results establish AKAP95 as a novel and mostly positive regulator of pre-mRNA splicing and a possible integrator of transcription and splicing regulation, and support a model that AKAP95 regulates pre-mRNA splicing via through scaffolding RNAs and RNA processing factors and facilitating the splice site communication.
2016-09-08 | GSE81916 | GEO
Project description: Not available
| S-EPMC5105168 | biostudies-literature
Project description:Set of experiments done on yeast deletion strains of various non-essential mRNA processing factors. Keywords = splicing
2010-05-27 | E-GEOD-35 | biostudies-arrayexpress
Project description:Set of experiments done on yeast deletion strains of various non-essential mRNA processing factors. Keywords = splicing Keywords: repeat sample
2002-04-16 | GSE35 | GEO
Project description:Cis-SAGe fusion RNAs in transcription splicing factors knocking-down 293T cells
| PRJNA451102 | ENA
Project description:Alternative cleavage and polyadenylation (APA) results in mRNA isoforms containing different 3’ untranslated regions (3’UTRs) and/or coding sequences. How core cleavage and polyadenylation (C/P) factors regulate APA is not well understood. Using siRNA knockdown coupled with deep sequencing, we found that several C/P factors can play significant roles in 3’UTR-APA. Whereas Pcf11 and Fip1 enhance usage of proximal poly(A) sites (pAs), CFI-25/68, PABPN1, and PABPC1 promote usage of distal pAs. Strong cis element biases were found for pAs regulated by CFI or Fip1, and the distance between pAs plays an important role in APA regulation. In addition, intronic pAs are substantially regulated by splicing factors, with U1 mostly influencing C/P events in 5’ introns and U2 impacting those in efficiently spliced introns. Furthermore, PABPN1 regulates expression of transcripts with pAs near the transcription start site, a property possibly related to its role in RNA degradation. Finally, we found that groups of APA events regulated by C/P factors are also modulated in cell differentiation and development with distinct trends. Together, our results indicate that the abundance of different C/P factors and splicing factors plays diverse roles in APA, and is relevant to APA regulation in biological conditions. knockdown experiments of 23 C/P factors, 3 splicing factors and U1D in mouse C2C12 myoblast cells
2015-04-01 | E-GEOD-62001 | biostudies-arrayexpress
Project description:All classes of RNA undergo processing. The two largest RNA processing complexes are those involved in rRNA biogenesis and mRNA splicing. Because of their complexity and essential roles, it has been difficult to dissect the functional interactions within these machines as well as to identify possible cross-talk with other steps in gene expression. Here we report the results of a high-density, quantitative genetic interaction map comprising 107,155 individual interactions involving 552 mutants, 166 of which are hypomorphic alleles of essential genes (This data is available at The Krogan Lab Interactome Database). Our data allow unique insights into the functional organization of the RNA processing machines. For example, we identify unexpected connections involving a component of the 19S proteasome, Sem1/Dss1. We show that Sem1 has genetic, physical and functional interactions with the mRNA export complex, Thp1-Sac3; it also interacts physically with a putative component of the COP9 signalosome, Csn12. We show using splicing-specific microarrays that Csn12 has an unanticipated role in mRNA splicing. Finally, we demonstrate the utility of this dataset in determining functions for uncharacterized ORFs. We show that deletion of the uncharacterized YNR004W causes a very similar splicing defect to that caused by deletion of TGS1, the enzyme that trimethylates the caps of snRNAs and snoRNAs. Keywords: E-MAP, RNA Processing, splicing, splicing-specific microarray, CSN12, COP9 signalosome Splicing-specific microarrays were used to assay the changes to splicing caused by deletion of several non-essential genes which had no previously characterized role in mRNA splicing but were suggested to be involved in this process by high-throughput genetic and/or protein-protein interaction data in Saccharomyces cerevisiae. The data includes samples collected from some mutants in log phase growth at 30 degrees C and from some mutants shifted to 16 degrees C, all competitively hybridized against wild type samples collected under the same conditions. .
2008-12-30 | E-GEOD-11634 | biostudies-arrayexpress
Project description:Budding yeast mRNA export and processing factors
| PRJNA144365 | ENA
Project description:The dynamic regulation of transcriptome requires coordinated participation of multiple RNA binding proteins (RBPs) in RNA processing. Dysregulated RNA processing, such as aberrant alternative splicing, is implicated in many cancers. Therefore, it is critical to explore the cancer-related RNA processing regulation and the underlying mechanisms. Many RBPs lack classical RNA-binding domains and their functions in RNA processing regulation remain unclear. Through an unbiased transcriptome-wide analysis, we report DAP3 binds ubiquitously to endogenous RNAs in vivo and its depletion reshapes the alternative splicing landscape in cancer cells. Mechanistically, we show DAP3 coordinates splicing regulatory networks, not only via mediating the formation of ribonucleoprotein (RNP) complexes, but also via modulating splicing of numerous splicing factors. Specific DAP3-regulated splicing changes such as non-productive splicing of WSB1 and RBM6, play important roles in tumorigenesis. Together, these findings provide critical mechanistic insights into the molecular functions of DAP3 in cancer development as a master regulator of RNA processing.
2022-02-10 | GSE172078 | GEO
Project description:Primary telomerase RNA transcripts are processed into shorter mature forms that assemble into a complex with the catalytic subunit and provide the template for telomerase activity. In diverse fungi telomerase RNA 3â end processing involves a single cleavage reaction by the spliceosome akin to the first step of splicing. Longer forms of human telomerase RNA (hTR) have been reported, but how the mature form of precisely 451 nucleotides is generated is still unknown. We now show that the splicing inhibitor isoginkgetin causes accumulation of long hTR transcripts, but find no evidence for a direct role for splicing in hTR processing. Instead, isoginkgetin mimics the effects of inhibiting the RNA exosome. Depletion of exosome components and accessory factors reveals functions for the cap binding complex (CBC) and the nuclear exosome targeting (NEXT) complex in hTR turnover. Whereas longer transcripts are predominantly degraded, shorter precursor RNAs are oligo-adenylated by TRF4-2 and either processed by poly (A) specific ribonuclease (PARN) or degraded by the exosome. Our results reveal that hTR biogenesis involves a kinetic competition between RNA processing and quality control pathways and suggest new treatment options for dyskeratosis congenita caused by mutations in RNA processing factors. We cloned and sequenced 3â ends by RLM-RACE coupled with high-throughput sequencing to gain further insights into hTR processing.
2015-11-25 | E-GEOD-73776 | biostudies-arrayexpress