Mutations in the large subunit of U2AF disrupt pre-mRNA splicing, cell cycle progression and nuclear structure

TC4, a ras-like G protein, has been implicated in the feedback pathway linking the onset of mitosis to the completion of DNA replication. In this report we find distinct roles for TC4 in both nuclear assembly and cell cycle progression. Mutant and wild-type forms of TC4 were added to Xenopus egg extracts capable of assembling nuclei around chromatin templates in vitro. We found that a mutant TC4 protein defective in GTP binding (GDP-bound form) suppressed nuclear growth and prevented DNA replication. Nuclear transport under these conditions approximated normal levels. In a separate set of experiments using a cell-free extract of Xenopus eggs that cycles between S and M phases, the GDP-bound form of TC4 had dramatic effects, blocking entry into mitosis even in the complete absence of nuclei. The effect of this mutant TC4 protein on cell cycle progression is mediated by phosphorylation of p34cdc2 on tyrosine and threonine residues, negatively regulating cdc2 kinase activity. Therefore, we provide direct biochemical evidence for a role of TC4 in both maintaining nuclear structure and in the signaling pathways that regulate entry into mitosis.

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Role of large subunit ribosomal protein L4 in ribosome maturation and cell cycle progression in Saccharomyces cerevisiae

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.491.9 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Ananth S Bommakanti ◽

Lasse Lindahl ◽

Janice M Zengel

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Ribosomal Protein ◽

Cell Cycle Progression ◽

Large Subunit ◽

Cycle Progression

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SiSTL1, encoding a large subunit of ribonucleotide reductase, is crucial for plant growth, chloroplast biogenesis, and cell cycle progression in Setaria italica

Journal of Experimental Botany ◽

10.1093/jxb/ery429 ◽

2018 ◽

Vol 70 (4) ◽

pp. 1167-1182

Author(s):

Chanjuan Tang ◽

Sha Tang ◽

Shuo Zhang ◽

Mingzhao Luo ◽

Guanqing Jia ◽

...

Keyword(s):

Cell Cycle ◽

Plant Growth ◽

Ribonucleotide Reductase ◽

Cell Cycle Progression ◽

Large Subunit ◽

Setaria Italica ◽

Chloroplast Biogenesis ◽

Cycle Progression

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Son Is Essential for Nuclear Speckle Organization and Cell Cycle Progression

Molecular Biology of the Cell ◽

10.1091/mbc.e09-02-0126 ◽

2010 ◽

Vol 21 (4) ◽

pp. 650-663 ◽

Cited By ~ 53

Author(s):

Alok Sharma ◽

Hideaki Takata ◽

Kei-ichi Shibahara ◽

Athanasios Bubulya ◽

Paula A. Bubulya

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Mrna Processing ◽

Mrna Splicing ◽

Scaffolding Protein ◽

Splicing Factors ◽

Nuclear Speckles ◽

Intact Cells ◽

Cycle Progression ◽

Processing Factors

Subnuclear organization and spatiotemporal regulation of pre-mRNA processing factors is essential for the production of mature protein-coding mRNAs. We have discovered that a large protein called Son has a novel role in maintaining proper nuclear organization of pre-mRNA processing factors in nuclear speckles. The primary sequence of Son contains a concentrated region of multiple unique tandem repeat motifs that may support a role for Son as a scaffolding protein for RNA processing factors in nuclear speckles. We used RNA interference (RNAi) approaches and high-resolution microscopy techniques to study the functions of Son in the context of intact cells. Although Son precisely colocalizes with pre-mRNA splicing factors in nuclear speckles, its depletion by RNAi leads to cell cycle arrest in metaphase and causes dramatic disorganization of small nuclear ribonuclear protein and serine-arginine rich protein splicing factors during interphase. Here, we propose that Son is essential for appropriate subnuclear organization of pre-mRNA splicing factors and for promoting normal cell cycle progression.

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DLP, a Novel Dim1 Family Protein Implicated in Pre-mRNA Splicing and Cell Cycle Progression

Journal of Biological Chemistry ◽

10.1074/jbc.m402522200 ◽

2004 ◽

Vol 279 (31) ◽

pp. 32839-32847 ◽

Cited By ~ 14

Author(s):

Xiaojing Sun ◽

Hua Zhang ◽

Dan Wang ◽

Dalong Ma ◽

Yan Shen ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Mrna Splicing ◽

Cycle Progression ◽

Family Protein

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Genetic and Physical Interactions Between Factors Involved in Both Cell Cycle Progression and Pre-mRNA Splicing inSaccharomyces cerevisiae

Genetics ◽

10.1093/genetics/156.4.1503 ◽

2000 ◽

Vol 156 (4) ◽

pp. 1503-1517 ◽

Cited By ~ 2

Author(s):

Sigal Ben-Yehuda ◽

Ian Dix ◽

Caroline S Russell ◽

Margaret McGarvey ◽

Jean D Beggs ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Synthetic Lethality ◽

Mrna Splicing ◽

Splicing Factors ◽

Restrictive Temperature ◽

Cycle Progression ◽

Cellular Processes ◽

Physical Interactions ◽

Mutant Cells

AbstractThe PRP17/CDC40 gene of Saccharomyces cerevisiae functions in two different cellular processes: pre-mRNA splicing and cell cycle progression. The Prp17/Cdc40 protein participates in the second step of the splicing reaction and, in addition, prp17/cdc40 mutant cells held at the restrictive temperature arrest in the G2 phase of the cell cycle. Here we describe the identification of nine genes that, when mutated, show synthetic lethality with the prp17/cdc40Δ allele. Six of these encode known splicing factors: Prp8p, Slu7p, Prp16p, Prp22p, Slt11p, and U2 snRNA. The other three, SYF1, SYF2, and SYF3, represent genes also involved in cell cycle progression and in pre-mRNA splicing. Syf1p and Syf3p are highly conserved proteins containing several copies of a repeated motif, which we term RTPR. This newly defined motif is shared by proteins involved in RNA processing and represents a subfamily of the known TPR (tetratricopeptide repeat) motif. Using two-hybrid interaction screens and biochemical analysis, we show that the SYF gene products interact with each other and with four other proteins: Isy1p, Cef1p, Prp22p, and Ntc20p. We discuss the role played by these proteins in splicing and cell cycle progression.

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Requirement and functional redundancy of two large ribonucleotide reductase subunit genes for cell cycle, chloroplast biogenesis in tomato

10.1101/2020.05.18.102301 ◽

2020 ◽

Author(s):

Mengjun Gu ◽

Yi Liu ◽

Man Cui ◽

Huilan Wu ◽

Hong-Qing Ling

Keyword(s):

Cell Cycle ◽

Ribonucleotide Reductase ◽

Cell Cycle Progression ◽

De Novo ◽

Large Subunit ◽

Chloroplast Biogenesis ◽

Tomato Genome ◽

Cycle Progression ◽

Tomato Growth ◽

Regulation Of Cell Cycle

AbstractRibonucleotide reductase (RNR), functioning in the de novo synthesis of dNTPs, is crucial for DNA replication and cell cycle progression. However, the knowledge about the RNR in plants is still limited. In this study, we isolated ylc1 (young leaf chlorosis 1) mutant, which exhibited many development defects such as dwarf stature, chlorotic young leaf, and smaller fruits. Map-based cloning, complementation, and knocking-out experiments confirmed that YLC1 encodes a large subunit of RNR (SlRNRL1), an enzyme involved in the de novo biosynthesis of dNTPs. Physiological and transcriptomic analyses indicate that SlRNRL1 plays a crucial role in the regulation of cell cycle, chloroplast biogenesis, and photosynthesis in tomato. In addition, we knocked out SlRNRL2 (a SlRNRL1 homolog) using CRISPR-Cas9 technology in the tomato genome, and found that SlRNRL2, possessing a redundant function with SlRNRL1, played a weak role in the formation of RNR complex due to its low expression intensity. Genetic analysis reveals that SlRNRL1 and SlRNRL2 are essential for tomato growth and development as the double mutant slrnrl1slrnrl2 is lethal. This also implies that the de novo synthesis of dNTPs is required for seed development in tomato. Overall, our results provide a new insight for understanding the SlRNRL1 and SlRNRL2 functions and the mechanism of de novo biosynthesis of dNTPs in plants.

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