scholarly journals Mutagenesis of ARS2 Domains To Assess Possible Roles in Cell Cycle Progression and MicroRNA and Replication-Dependent Histone mRNA Biogenesis

2015 ◽  
Vol 35 (21) ◽  
pp. 3753-3767 ◽  
Author(s):  
Connor O'Sullivan ◽  
Jennifer Christie ◽  
Marcus Pienaar ◽  
Jake Gambling ◽  
Philip E. B. Nickerson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase Ii ◽  
Cell Cycle Progression ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Histone Mrna ◽  
Cycle Progression ◽  
Transcript Processing ◽  
C Terminus ◽  
Domain Of Unknown Function

ARS2 is a regulator of RNA polymerase II transcript processing through its role in the maturation of distinct nuclear cap-binding complex (CBC)-controlled RNA families. In this study, we examined ARS2 domain function in transcript processing. Structural modeling based on the plant ARS2 orthologue, SERRATE, revealed 2 previously uncharacterized domains in mammalian ARS2: an N-terminal domain of unknown function (DUF3546), which is also present in SERRATE, and an RNA recognition motif (RRM) that is present in metazoan ARS2 but not in plants. Both the DUF3546 and zinc finger domain (ZnF) were required for association with microRNA and replication-dependent histone mRNA. Mutations in the ZnF disrupted interaction with FLASH, a key component in histone pre-mRNA processing. Mutations targeting the Mid domain implicated it in DROSHA interaction and microRNA biogenesis. The unstructured C terminus was required for interaction with the CBC protein CBP20, while the RRM was required for cell cycle progression and for binding to FLASH. Together, our results support a bridging model in which ARS2 plays a central role in RNA recognition and processing through multiple protein and RNA interactions.

scholarly journals The RNA recognition motif of NIFK is required for rRNA maturation during cell cycle progression

RNA Biology ◽  
2015 ◽  
Vol 12 (3) ◽  
pp. 255-267 ◽  
Author(s):  
Wen-An Pan ◽  
Hsin-Yue Tsai ◽  
Shun-Chang Wang ◽  
Michael Hsiao ◽  
Pei-Yu Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Cycle Progression ◽  
Recognition Motif ◽  
Rrna Maturation

scholarly journals Regulation of CDK7–Carboxyl-Terminal Domain Kinase Activity by the Tumor Suppressor p16INK4A Contributes to Cell Cycle Regulation

2000 ◽  
Vol 20 (20) ◽  
pp. 7726-7734 ◽  
Author(s):  
Eiji Nishiwaki ◽  
Saralinda L. Turner ◽  
Susanna Harju ◽  
Shiro Miyazaki ◽  
Masahide Kashiwagi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Rna Polymerase Ii ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Alternative Pathway ◽  
Cycle Progression ◽  
Terminal Domain ◽  
Carboxyl Terminal Domain ◽  
Carboxyl Terminal

ABSTRACT The eukaryotic cell cycle is regulated by cyclin-dependent kinases (CDKs). CDK4 and CDK6, which are activated by D-type cyclins during the G1 phase of the cell cycle, are thought to be responsible for phosphorylation of the retinoblastoma gene product (pRb). The tumor suppressor p16INK4A inhibits phosphorylation of pRb by CDK4 and CDK6 and can thereby block cell cycle progression at the G1/S boundary. Phosphorylation of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II by general transcription factor TFIIH is believed to be an important regulatory event in transcription. TFIIH contains a CDK7 kinase subunit and phosphorylates the CTD. We have previously shown that p16INK4A inhibits phosphorylation of the CTD by TFIIH. Here we report that the ability of p16INK4A to inhibit CDK7-CTD kinase contributes to the capacity to induce cell cycle arrest. These results suggest that p16INK4A may regulate cell cycle progression by inhibiting not only CDK4-pRb kinase activity but also by modulating CDK7-CTD kinase activity. Regulation of CDK7-CTD kinase activity by p16INK4A thus may represent an alternative pathway for controlling cell cycle progression.

scholarly journals Cyclin D-Cdk4,6 drives cell cycle progression via the retinoblastoma protein’s C-terminal helix

2018 ◽  
Author(s):  
Benjamin R. Topacio ◽  
Evgeny Zatulovskiy ◽  
Sandra Cristea ◽  
Shicong Xie ◽  
Carrie S. Tambo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Cycle Progression ◽  
Alpha Helix ◽  
G1 Arrest ◽  
Cyclin D ◽  
Cycle Progression ◽  
C Terminus ◽  
Docking Mechanism ◽  
Tumor Suppressive Function

SummaryThe cyclin-dependent kinases Cdk4 and Cdk6 form complexes with D-type cyclins to drive cell proliferation. A well-known target of cyclin D-Cdk4,6 is the retinoblastoma protein, Rb, which inhibits cell cycle progression until its inactivation by phosphorylation. However, the role of cyclin D-Cdk4,6 phosphorylation of Rb in cell cycle progression is unclear because Rb can be phosphorylated by other cyclin-Cdk complexes and cyclin D-Cdk4,6 complexes have other targets that may drive cell division. Here, we show that cyclin D-Cdk4,6 docks one side of an alpha-helix in the C-terminus of Rb, which is not recognized by cyclins E, A, and B. This helix-based docking mechanism is shared by the p107 and p130 Rb-family members across metazoans. Mutation of the Rb C-terminal helix prevents phosphorylation, promotes G1 arrest, and enhances Rb’s tumor suppressive function. Our work conclusively demonstrates that the cyclin D-Rb interaction drives cell division and defines a new class of cyclin-based docking mechanisms.

scholarly journals Mdt1, a Novel Rad53 FHA1 Domain-Interacting Protein, Modulates DNA Damage Tolerance and G2/M Cell Cycle Progression in Saccharomycescerevisiae

2004 ◽  
Vol 24 (7) ◽  
pp. 2779-2788 ◽  
Author(s):  
Brietta L. Pike ◽  
Suganya Yongkiettrakul ◽  
Ming-Daw Tsai ◽  
Jörg Heierhorst
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Progression ◽  
Structural Integrity ◽  
Damage Tolerance ◽  
Rna Recognition Motif ◽  
M Cell ◽  
Dna Damage Tolerance ◽  
Cycle Progression ◽  
Dependent Cell

ABSTRACT The Rad53 kinase plays a central role in yeast DNA damage checkpoints. Rad53 contains two FHA phosphothreonine-binding domains that are required for Rad53 activation and possibly downstream signaling. Here we show that the N-terminal Rad53 FHA1 domain interacts with the RNA recognition motif, coiled-coil, and SQ/TQ cluster domain-containing protein Mdt1 (YBl051C). The interaction of Rad53 and Mdt1 depends on the structural integrity of the FHA1 phosphothreonine-binding site as well as threonine-305 of Mdt1. Mdt1 is constitutively threonine phosphorylated and hyperphosphorylated in response to DNA damage in vivo. DNA damage-dependent Mdt1 hyperphosphorylation depends on the Mec1 and Tel1 checkpoint kinases, and Mec1 can directly phosphorylate a recombinant Mdt1 SQ/TQ domain fragment. MDT1 overexpression is synthetically lethal with a rad53 deletion, whereas mdt1 deletion partially suppresses the DNA damage hypersensitivity of checkpoint-compromised strains and generally improves DNA damage tolerance. In the absence of DNA damage, mdt1 deletion leads to delayed anaphase completion, with an elongated cell morphology reminiscent of that of G2/M cell cycle mutants. mdt1-dependent and DNA damage-dependent cell cycle delays are not additive, suggesting that they act in the same pathway. The data indicate that Mdt1 is involved in normal G2/M cell cycle progression and is a novel target of checkpoint-dependent cell cycle arrest pathways.

scholarly journals Cyclin C influences the timing of mitosis in fission yeast

2017 ◽  
Vol 28 (13) ◽  
pp. 1738-1744 ◽  
Author(s):  
Gabor Banyai ◽  
Zsolt Szilagyi ◽  
Vera Baraznenok ◽  
Olga Khorosjutina ◽  
Claes M. Gustafsson
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Rna Polymerase Ii ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Mediator Complex ◽  
Cycle Progression ◽  
Cyclin C ◽  
M Phase

The multiprotein Mediator complex is required for the regulated transcription of nearly all RNA polymerase II–dependent genes. Mediator contains the Cdk8 regulatory subcomplex, which directs periodic transcription and influences cell cycle progression in fission yeast. Here we investigate the role of CycC, the cognate cyclin partner of Cdk8, in cell cycle control. Previous reports suggested that CycC interacts with other cellular Cdks, but a fusion of CycC to Cdk8 reported here did not cause any obvious cell cycle phenotypes. We find that Cdk8 and CycC interactions are stabilized within the Mediator complex and the activity of Cdk8-CycC is regulated by other Mediator components. Analysis of a mutant yeast strain reveals that CycC, together with Cdk8, primarily affects M-phase progression but mutations that release Cdk8 from CycC control also affect timing of entry into S phase.

scholarly journals Inhibition of transcription blocks cell cycle progression of NIH3T3 fibroblasts specifically in G1

1993 ◽  
Vol 105 (1) ◽  
pp. 113-122 ◽  
Author(s):  
S. Adolph ◽  
S. Brusselbach ◽  
R. Muller
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Cell Cycle Progression ◽  
Video Recording ◽  
Cycle Progression ◽  
Nih3t3 Cells ◽  
Restriction Point ◽  
Alpha Amanitin

We have analysed the role of RNA polymerase II-dependent transcription in cell cycle progression. Time-lapse video recording and cytogenetic analysis were used to determine the sensitivity of NIH3T3 cells to the RNA polymerase II inhibitor alpha-amanitin at different stages of the cell cycle. Our results show that alpha-amanitin blocks cells specifically in G1, irrespective of the concentration within the range of 3 to 30 micrograms/ml. This indicates that transcription in G1 is required to overcome a restriction point located in this phase of the cell cycle. In agreement with this conclusion is the requirement for an uninhibited protein synthesis during G1 progression. In addition, the insensitivity of S-phase cells to RNA polymerase II inhibition suggests that the transcription of genes thought to be normally induced during S/G2 is not required for the completion of an ongoing cell cycle. S/G2 progression was however clearly dependent on protein synthesis. This suggests that cells exposed to alpha-amanitin are able to complete their cell cycle because sufficiently high levels of mRNA are present in S/G2 due to basal level transcription, or are left from preceding cell cycles. It is therefore unlikely that transcriptional regulation in S or G2 plays a crucial role in the control of cell cycle progression in NIH3T3 cells.

scholarly journals The G2-phase enriched lncRNA SNHG26 is necessary for proper cell cycle progression and proliferation

2021 ◽  
Author(s):  
Helle Samdal ◽  
Siv A. Hegre ◽  
Konika Chawla ◽  
Nina-Beate Liabakk ◽  
Per A. Aas ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase Ii ◽  
Cell Cycle Progression ◽  
Phase Distribution ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
Cycle Progression ◽  
Chip Sequencing ◽  
Cell Cycle Phase Distribution ◽  
Regulation Of Cell Cycle

AbstractLong noncoding RNAs (lncRNAs) are involved in the regulation of cell cycle, although only a few have been functionally characterized. By combining RNA sequencing and ChIP sequencing of cell cycle synchronized HaCaT cells we have previously identified lncRNAs highly enriched for cell cycle functions. Based on a cyclic expression profile and an overall high correlation to histone 3 lysine 4 trimethylation (H3K4me3) and RNA polymerase II (Pol II) signals, the lncRNA SNHG26 was identified as a top candidate. In the present study we report that downregulation of SNHG26 affects mitochondrial stress, proliferation, cell cycle phase distribution, and gene expression in cis- and in trans, and that this effect is reversed by upregulation of SNHG26. We also find that the effect on cell cycle phase distribution is cell type specific and stable over time. Results indicate an oncogenic role of SNHG26, possibly by affecting cell cycle progression through the regulation of downstream MYC-responsive genes.

scholarly journals Human Transcription Factor hTAFII150 (CIF150) Is Involved in Transcriptional Regulation of Cell Cycle Progression

1999 ◽  
Vol 19 (8) ◽  
pp. 5548-5556 ◽  
Author(s):  
Jay Martin ◽  
Robert Halenbeck ◽  
Jörg Kaufmann
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Cell Cycle Progression ◽  
Core Promoter ◽  
Cyclin B1 ◽  
Cycle Progression ◽  
Mammalian Cell Lines ◽  
Human Transcription Factor

ABSTRACT Here we present evidence that CIF150 (hTAFII150), the human homolog of Drosophila TAFII150, plays an important and selective role in establishing gene expression patterns necessary for progression through the cell cycle. Gel filtration experiments demonstrate that CIF150 (hTAFII150) seems to be less tightly associated with human transcription factor IID than hTAFII130 is associated with hTAFII250. The transient functional knockout of CIF150 (hTAFII150) protein led to cell cycle arrest at the G2/M transition in mammalian cell lines. PCR display analysis with the RNA derived from CIF150-depleted cells indicated that CIF150 (hTAFII150) is required for the transcription of only a subset of RNA polymerase II genes. CIF150 (hTAFII150) directly stimulated cyclin B1 and cyclin A transcription in cotransfection assays and in vitro assays, suggesting that the expression of these genes is dependent on CIF150 (hTAFII150) function. We defined a CIF150 (hTAFII150) consensus binding site and demonstrated that a CIF150-responsive cis element is present in the cyclin B1 core promoter. These results suggest that one function of CIF150 (hTAFII150) is to select specific RNA polymerase II core promoter elements involved in cell cycle progression.

scholarly journals The C terminus of talin links integrins to cell cycle progression

2011 ◽  
Vol 195 (3) ◽  
pp. 499-513 ◽  
Author(s):  
Pengbo Wang ◽  
Christoph Ballestrem ◽  
Charles H. Streuli
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Focal Adhesion ◽  
Intracellular Signaling ◽  
Cell Cycle Progression ◽  
Mammary Epithelial Cells ◽  
Dependent Manner ◽  
Cycle Progression ◽  
Cell Fate Decisions ◽  
C Terminus

Integrins are cell adhesion receptors that sense the extracellular matrix (ECM) environment. One of their functions is to regulate cell fate decisions, although the question of how integrins initiate intracellular signaling is not fully resolved. In this paper, we examine the role of talin, an adapter protein at cell–matrix attachment sites, in outside-in signaling. We used lentiviral small hairpin ribonucleic acid to deplete talin in mammary epithelial cells. These cells still attached to the ECM in an integrin-dependent manner and spread. They had a normal actin cytoskeleton, but vinculin, paxillin, focal adhesion kinase (FAK), and integrin-linked kinase were not recruited to adhesion sites. Talin-deficient cells showed proliferation defects, and reexpressing a tail portion of the talin rod, but not its head domain, restored integrin-mediated FAK phosphorylation, suppressed p21 expression, and rescued cell cycle. Thus, talin recruits and activates focal adhesion proteins required for proliferation via the C terminus of its rod domain. Our study reveals a new function for talin, which is to link integrin adhesions with cell cycle progression.

scholarly journals POLR2A Promotes the Proliferation of Gastric Cancer Cells by Advancing the Overall Cell Cycle Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiuyu Jiang ◽  
Jinyuan Zhang ◽  
Fang Li ◽  
Xiaoping Ma ◽  
Fei Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Gastric Cancer Cells ◽  
Cycle Progression

RNA polymerase II subunit A (POLR2A) is the largest subunit encoding RNA polymerase II and closely related to cancer progression. However, the biological role and underlying molecular mechanism of POLR2A in gastric cancer (GC) are still unclear. Our study demonstrated that POLR2A was highly expressed in GC tissue and promoted the proliferation of GC in vitro and in vivo. We also found that POLR2A participated in the transcriptional regulation of cyclins and cyclin-dependent kinases (CDKs) at each stage and promoted their expression, indicated POLR2A’s overall promotion of cell cycle progression. Moreover, POLR2A inhibited GC cell apoptosis and promoted GC cell migration. Our results indicate that POLR2A play an oncogene role in GC, which may be an important factor involved in the occurrence and development of GC.

Sign in / Sign up

Export Citation Format

Share Document