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Expression dynamics of periodic transcripts during cancer cell cycle progression and their correlation with anticancer drug sensitivity

ABSTRACT: Cell cycle is the center of cellular activities and is orchestrated by complex regulatory mechanisms, among which transcriptional regulation is one of the most important parts. Alternative splicing dramatically expands the regulatory network by producing transcript isoforms of genes to exquisitely control the cell cycle. However, the patterns of transcript isoform expression in the cell cycle are unclear. Therapies targeting cell cycle checkpoints are commonly used as anticancer therapies, but none of them were designed and have been evaluated at alternative splicing transcripts level. To explore alternative splicing patterns during cell cycle progression, we performed sequential transcriptomic assays following cell cycle synchronization in breast cancer MDA-MB-231 cell lines, used flow cytometry and reference cell cycle transcripts to confirm the cell cycle phases of samples.

ORGANISM(S): Homo sapiens

PROVIDER: GSE216497 | GEO | 2022/12/28

REPOSITORIES: GEO

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An extensive program of periodic alternative splicing linked to cell cycle progression

Project description:Progression through the mitotic cell cycle requires periodic regulation of gene function at the levels of transcription, translation, protein-protein interactions, post-translational modification and degradation. However, the role of alternative splicing (AS) in the temporal control of cell cycle is not well understood. By sequencing the human transcriptome through two continuous cell cycles, we identify ~1,300 genes with cell cycle-dependent AS changes. These genes are significantly enriched in functions linked to cell cycle control, yet they do not significantly overlap genes subject to periodic changes in steady-state transcript levels. Many of the periodically spliced genes are controlled by the SR protein kinase CLK1, whose level undergoes cell cycle-dependent fluctuations via an auto-inhibitory circuit. Disruption of CLK1 causes pleiotropic cell cycle defects and loss of proliferation, whereas CLK1 over-expression is associated with various cancers. These results thus reveal a large program of CLK1-regulated periodic AS intimately associated with cell cycle control.

2016-05-19 | GSE81485 | GEO

Ryu2017 - Generic human genome-scale metabolic model (Recon 2M.2)

Project description:Recon 2M.2 is a generic genome-scale metabolic model of Homo sapiens, in which a framework for gene-transcript-protein-reaction associations (GeTPRA) was deployed to generate metabolic reactions by considering the effects of alternative splicing of metabolic genes (i.e., both principal and non-principal transcripts). Eight versions of COBRA-compliant SBML files are available for Recon 2M.2 depending on the use of: MNXref versus BiGG IDs (metabolite IDs); Entrez gene IDs (GPR associations) versus Ensembl transcript IDs versus RefSeq transcript IDs versus UCSC transcript IDs (TPR associations for the last three database IDs).

2022-05-16 | MODEL2205110002 | BioModels

An extensive program of periodic alternative splicing linked to cell cycle progression

| OEX000085 | NODE

Single-cell RNA-seq Uncovers Dynamic Processes and Critical Regulators in Mouse Spermatogenesis

Project description:A systematic interrogation of male germ cells is key to complete understanding of molecular mechanisms governing spermatogenesis and the development of new strategies for infertility therapies and male contraception. Here we develop an approach to purify all types of homogeneous spermatogenic cells by combining transgenic labelling and synchronization of the cycle of the seminiferous epithelium, and subsequent single-cell RNA-sequencing. We reveal extensive and previously uncharacterized dynamic processes and molecular signatures in gene expression, as well as specific patterns of alternative splicing, and novel regulators for specific stages of male germ cell development. Our transcriptomics analyses led us to discover discriminative markers for isolating specific stages of round spermatids, and identify different embryo developmental potential between early and late stage spermatids, providing evidence that maturation of round spermatids impacts on embryo development. This work provides valuable insights into mammalian spermatogenesis, and a comprehensive resource for the complete elucidation of gametogenesis.

2018-08-01 | GSE107644 | GEO

Cell cycle and G1 cyclins

Project description:This SuperSeries is composed of the following subset Series: GSE29800: Lack of G1 cyclin arrest cell cycle synchronization time-course microarray in Glucose GSE29892: Alpha Factor arrest cell cycle synchronization time-course microarray in Galactose GSE29893: Alpha Factor arrest cell cycle synchronization time-course microarray in Glucose Refer to individual Series

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RNA-seq analysis in breast cancer cell lines BT549 WT and SF3A3 5'UTR DSL3 edited.

Project description:Splicing is a central RNA-based process commonly altered in human cancers; however, how the splicing machinery is co-opted during tumorigenesis remains largely unresolved. Here we identify the splice factor SF3A3 at the nexus of an oncogenic translation program that rewires splicing to promote tumorigenesis. Our results suggest that key spliceosomal networks centered on the essential core U2-associated factor, SF3A3, are exquisitely controlled at the translation level during oncogenic stress. Upon oncogene activation, SF3A3 translation is rapidly enabled via a conserved internal stem-loop structure embedded in the transcript 5’ untranslated region (UTR). Uncoupled SF3A3 translation leads to alternative splicing of several mRNAs involved in mitochondrial dynamics, and induces a metabolic switch that fuels cancer initiation properties in MYC-driven breast tumorigenesis in vivo. Finally, we compelling show that SF3A3 is post-transcriptionally altered and predicts for poor prognosis in aggressive triple negative breast cancers. Together, these findings unveil a highly dynamic regulatory network that interfaces mRNA splicing and translation to orchestrate cancer gene expression networks.

2021-03-25 | GSE151529 | GEO

RNA-seq analysis in fibroblast IMR90 CTRL/MYC/MYC+SF3A3 KD

2021-03-25 | GSE147505 | GEO

Global Regulation of Alternative RNA Splicing by the SR-Rich Protein RBM39 CLIP-seq

Project description:RBM39 is extensively involved in alternative splicing of RNA and helps regulate transcript levels. RBM39 may modulate alternative splicing similarly to U2AF65 by either directly binding to RNA or recruiting other splicing factors, such as U2AF65.

2017-07-20 | GSE101631 | GEO

Global Regulation of Alternative RNA Splicing by the SR-Rich Protein RBM39

2016-09-13 | GSE86846 | GEO

Genome-wide analysis of alternative splicing in Zea mays: landscape and genetic regulation

Project description:Analysis of the maize alternative splicing landscape, including transcript discovery and mapping of genotype-dependent variations in alternative splicing using B73, Mo17 and the SX19 inbred mapping population

2014-10-29 | GSE57337 | GEO

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