scholarly journals Roles of CDK/Cyclin complexes in transcription and pre-mRNA splicing: Cyclins L and CDK11 at the cross-roads of cell cycle and regulation of gene expression

2020 ◽  
Vol 107 ◽  
pp. 36-45 ◽  
Author(s):  
Pascal Loyer ◽  
Janeen H. Trembley
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Regulation Of Gene Expression ◽  
Mrna Splicing ◽  
The Cross

scholarly journals STAU2 protein level is controlled by caspases and the CHK1 pathway and regulates cell cycle progression in the non-transformed hTERT-RPE1 cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lionel Condé ◽  
Yulemi Gonzalez Quesada ◽  
Florence Bonnet-Magnaval ◽  
Rémy Beaujois ◽  
Luc DesGroseillers
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Steady State ◽  
Posttranscriptional Regulation ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Cycle Progression

AbstractBackgroundStaufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from theSTAU2gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation.ResultsCRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway for 4 h dissociates STAU2 from proteins involved in translation and RNA metabolism.ConclusionsThese results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. The mechanism by which STAU2 regulates cell growth likely involves caspases and the kinase CHK1 pathway.

scholarly journals Spatial transcriptome profiling by MERFISH reveals subcellular RNA compartmentalization and cell cycle-dependent gene expression

2019 ◽  
Vol 116 (39) ◽  
pp. 19490-19499 ◽  
Author(s):  
Chenglong Xia ◽  
Jean Fan ◽  
George Emanuel ◽  
Junjie Hao ◽  
Xiaowei Zhuang
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Spatial Information ◽  
Detection Efficiency ◽  
Expression Profiles ◽  
Regulation Of Gene Expression ◽  
Rna Profiling ◽  
Spatially Resolved ◽  
Cycle Dependent

The expression profiles and spatial distributions of RNAs regulate many cellular functions. Image-based transcriptomic approaches provide powerful means to measure both expression and spatial information of RNAs in individual cells within their native environment. Among these approaches, multiplexed error-robust fluorescence in situ hybridization (MERFISH) has achieved spatially resolved RNA quantification at transcriptome scale by massively multiplexing single-molecule FISH measurements. Here, we increased the gene throughput of MERFISH and demonstrated simultaneous measurements of RNA transcripts from ∼10,000 genes in individual cells with ∼80% detection efficiency and ∼4% misidentification rate. We combined MERFISH with cellular structure imaging to determine subcellular compartmentalization of RNAs. We validated this approach by showing enrichment of secretome transcripts at the endoplasmic reticulum, and further revealed enrichment of long noncoding RNAs, RNAs with retained introns, and a subgroup of protein-coding mRNAs in the cell nucleus. Leveraging spatially resolved RNA profiling, we developed an approach to determine RNA velocity in situ using the balance of nuclear versus cytoplasmic RNA counts. We applied this approach to infer pseudotime ordering of cells and identified cells at different cell-cycle states, revealing ∼1,600 genes with putative cell cycle-dependent expression and a gradual transcription profile change as cells progress through cell-cycle stages. Our analysis further revealed cell cycle-dependent and cell cycle-independent spatial heterogeneity of transcriptionally distinct cells. We envision that the ability to perform spatially resolved, genome-wide RNA profiling with high detection efficiency and accuracy by MERFISH could help address a wide array of questions ranging from the regulation of gene expression in cells to the development of cell fate and organization in tissues.

scholarly journals Continued withdrawal from the cell cycle and regulation of cellular genes in mouse erythroleukemia cells blocked in differentiation by the c-myc oncogene.

1989 ◽  
Vol 9 (4) ◽  
pp. 1714-1720 ◽  
Author(s):  
J A Coppola ◽  
J M Parker ◽  
G D Schuler ◽  
M D Cole
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Control ◽  
Regulation Of Gene Expression ◽  
Constitutive Expression ◽  
Housekeeping Genes ◽  
Cell System ◽  
Myc Oncogene ◽  
Temporary Decrease ◽  
Mouse Erythroleukemia

Constitutive expression of the c-myc oncogene blocks dimethyl sulfoxide (DMSO)-induced differentiation of mouse erythroleukemia (MEL) cells. During the first 12 h of treatment with DMSO, MEL cells undergo a temporary decrease in the level of c-myc mRNA, followed by a temporary withdrawal from the cell cycle. We found the same shutoff of DNA synthesis during the first 12 to 30 h after DMSO induction in normal MEL cells (which differentiate) and in c-myc-transfected MEL cells (which do not differentiate). We also examined whether deregulated c-myc expression grossly interfered with the regulation of gene expression during MEL cell differentiation. We used run-on transcription assays to monitor the rate of transcription of four oncogenes (c-myc, c-myb, c-fos, and c-K-ras); all except c-K-ras showed a rapid but temporary decrease in transcription after induction in both c-myc-transfected and control cells. Finally, we found the same regulation of cytoplasmic mRNA expression in both types of cells for four oncogenes and three housekeeping genes associated with growth. We conclude that in the MEL cell system, the effects of deregulated c-myc expression do not occur through a disruption of cell cycle control early in induction, nor do they occur through gross deregulation of gene expression.

scholarly journals Differential expression of genes influencing mitotic processes in cord blood mononuclear cells after a pre-conceptional micronutrient-based randomized controlled trial: Pune Rural Intervention in Young Adolescents (PRIYA)

2021 ◽  
Author(s):  
Satyajeet P Khare ◽  
Ayush Madhok ◽  
Indumathi Patta ◽  
Krishna K Sukla ◽  
Vipul V Wagh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Vitamin B12 ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
Regulation Of Gene Expression ◽  
Cell Cycle Checkpoint ◽  
Nucleotide Synthesis ◽  
Blood Mononuclear Cells ◽  
Cord Blood Mononuclear Cells

In the Pune Maternal Nutrition Study, low maternal vitamin B12 and high folate concentrations during pregnancy predicted adiposity and insulin resistance (diabesity) in the children. Based on these findings, we designed an RCT (PRIYA) to provide these nutrients pre-conceptionally to reduce diabesity in the offspring. The interventions included: 1) vitamin B12+multi-micronutrients and protein supplement (B12+MMN), 2) vitamin B12 alone, and 3) placebo. A total of 149 women became pregnant and delivered in the trial. We report results of RNA sequencing in the cord-blood mononuclear cells in 88 deliveries. Gene expression analysis revealed 20 differentially expressed genes (FDR <0.1, a discovery threshold) between the B12+MMN and placebo groups. The enriched biological processes included: chromosome segregation, nuclear division and organelle fission. A cell cycle checkpoint gene Claspin (CLSPN) was expressed less in the B12+MMN group but proliferation markers did not differ. No difference was observed between the B12 alone and placebo groups. The B-complex vitamins are essential for nucleotide synthesis and generation of S-Adenosyl Methionine, a universal cellular methyl donor and thereby may contribute to the regulation of gene expression. Vitamins A and D, and zinc in MMN may also influence gene expression. We propose that the multi-micronutrient intervention influenced rate of progression of specific phases of cell cycle without affecting proliferation. Vitamin B12 alone was not sufficient. We highlight a novel molecular mechanism for the effect of multi-micronutrients during fetal development, and a plausible mechanism for intergenerational nutritional programming. Follow up studies will help understand their implications on the future phenotype.

Continued withdrawal from the cell cycle and regulation of cellular genes in mouse erythroleukemia cells blocked in differentiation by the c-myc oncogene

1989 ◽  
Vol 9 (4) ◽  
pp. 1714-1720
Author(s):  
J A Coppola ◽  
J M Parker ◽  
G D Schuler ◽  
M D Cole
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Control ◽  
Regulation Of Gene Expression ◽  
Constitutive Expression ◽  
Housekeeping Genes ◽  
Cell System ◽  
Myc Oncogene ◽  
Temporary Decrease ◽  
Mouse Erythroleukemia

Constitutive expression of the c-myc oncogene blocks dimethyl sulfoxide (DMSO)-induced differentiation of mouse erythroleukemia (MEL) cells. During the first 12 h of treatment with DMSO, MEL cells undergo a temporary decrease in the level of c-myc mRNA, followed by a temporary withdrawal from the cell cycle. We found the same shutoff of DNA synthesis during the first 12 to 30 h after DMSO induction in normal MEL cells (which differentiate) and in c-myc-transfected MEL cells (which do not differentiate). We also examined whether deregulated c-myc expression grossly interfered with the regulation of gene expression during MEL cell differentiation. We used run-on transcription assays to monitor the rate of transcription of four oncogenes (c-myc, c-myb, c-fos, and c-K-ras); all except c-K-ras showed a rapid but temporary decrease in transcription after induction in both c-myc-transfected and control cells. Finally, we found the same regulation of cytoplasmic mRNA expression in both types of cells for four oncogenes and three housekeeping genes associated with growth. We conclude that in the MEL cell system, the effects of deregulated c-myc expression do not occur through a disruption of cell cycle control early in induction, nor do they occur through gross deregulation of gene expression.

MeCP2 and CTCF: enhancing the cross-talk of silencers

2017 ◽  
Vol 95 (6) ◽  
pp. 593-608 ◽  
Author(s):  
Juan Ausió ◽  
Philippe T. Georgel
Keyword(s):  
Gene Expression ◽  
Rett Syndrome ◽  
Cross Talk ◽  
Regulation Of Gene Expression ◽  
Transcriptional Regulators ◽  
Functional Interactions ◽  
Recent Advances ◽  
Functional Aspects ◽  
The Cross ◽  
Introductory Review

This paper provides a brief introductory review of the most recent advances in our knowledge about the structural and functional aspects of two transcriptional regulators: MeCP2, a protein whose mutated forms are involved in Rett syndrome; and CTCF, a constitutive transcriptional insulator. This is followed by a description of the PTMs affecting these two proteins and an analysis of their known interacting partners. A special emphasis is placed on the recent studies connecting these two proteins, focusing on the still poorly understood potential structural and functional interactions between the two of them on the chromatin substrate. An overview is provided for some of the currently known genes that are dually regulated by these two proteins. Finally, a model is put forward to account for their possible involvement in their regulation of gene expression.

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