ArticlePloS one2012
Perturbation of chromatin structure globally affects localization and recruitment of splicing factors.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
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- Targeting the MALAT1 gene with the CRISPR/Cas9 technique in prostate cancer.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2022Article
- Nuclear Architecture in the Nervous System.Results and problems in cell differentiation · 2022Review
- An SR protein is essential for activating DNA repair in malaria parasites.Journal of cell science · 2021Article
- Contribution of advanced fluorescence nano microscopy towards revealing mitotic chromosome structure.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2021Review
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- Integrated Assessment of Viral Transcription, Antigen Presentation, and CD8Journal of virology · 2020Article
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- Silencing of MALAT1 inhibits migration and invasion by sponging miR‑1‑3p in prostate cancer cells.Molecular medicine reports · 2019Article
- Genome-wide methods for investigating long noncoding RNAs.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2019Review
- The chromatin remodeler ZmCHB101 impacts alternative splicing contexts in response to osmotic stress.Plant cell reports · 2019Article
- Protective paraspeckle hyper-assembly downstream of TDP-43 loss of function in amyotrophic lateral sclerosis.Molecular neurodegeneration · 2018Article
- Identification of novel PANDAR protein interaction partners involved in splicing regulation.Scientific reports · 2018Article
- The determinants of alternative RNA splicing in human cells.Molecular genetics and genomics : MGG · 2017Review
- Chromatin loops and causality loops: the influence of RNA upon spatial nuclear architecture.Chromosoma · 2017Review
- Article
- Post-transcriptional regulation of long noncoding RNAs in cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Review
- Sudemycin E influences alternative splicing and changes chromatin modifications.Nucleic acids research · 2014Article
- Zinc-finger protein ZFP318 is essential for expression of IgD, the alternatively spliced Igh product made by mature B lymphocytes.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Chromatin structure is an important factor in the functional coupling between transcription and mRNA processing, not only by regulating alternative splicing events, but also by contributing to exon recognition during constitutive splicing. We observed that depolarization of neuroblastoma cell membrane potential, which triggers general histone acetylation and regulates alternative splicing, causes a concentration of SR proteins in nuclear speckles. This prompted us to analyze the effect of chromatin structure on splicing factor distribution and dynamics. Here, we show that induction of histone hyper-acetylation results in the accumulation in speckles of multiple splicing factors in different cell types. In addition, a similar effect is observed after depletion of the heterochromatic protein HP1α, associated with repressive chromatin. We used advanced imaging approaches to analyze in detail both the structural organization of the speckle compartment and nuclear distribution of splicing factors, as well as studying direct interactions between splicing factors and their association with chromatin in vivo. The results support a model where perturbation of normal chromatin structure decreases the recruitment efficiency of splicing factors to nascent RNAs, thus causing their accumulation in speckles, which buffer the amount of free molecules in the nucleoplasm. To test this, we analyzed the recruitment of the general splicing factor U2AF65 to nascent RNAs by iCLIP technique, as a way to monitor early spliceosome assembly. We demonstrate that indeed histone hyper-acetylation decreases recruitment of U2AF65 to bulk 3' splice sites, coincident with the change in its localization. In addition, prior to the maximum accumulation in speckles, ∼20% of genes already show a tendency to decreased binding, while U2AF65 seems to increase its binding to the speckle-located ncRNA MALAT1. All together, the combined imaging and biochemical approaches support a model where chromatin structure is essential for efficient co-transcriptional recruitment of general and regulatory splicing factors to pre-mRNA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.