Phenotypic analysis of Paf1/RNA polymerase II complex mutations reveals connections to cell cycle regulation, protein synthesis, and lipid and nucleic acid metabolism

2002 ◽  
Vol 268 (2) ◽  
pp. 272-285 ◽  
Author(s):  
J. Betz ◽  
M. Chang ◽  
T. Washburn ◽  
S. Porter ◽  
C. Mueller ◽  
...  
2012 ◽  
Vol 44 (16) ◽  
pp. 811-818 ◽  
Author(s):  
Michael Oster ◽  
Eduard Murani ◽  
Cornelia C. Metges ◽  
Siriluck Ponsuksili ◽  
Klaus Wimmers

Inadequate maternal protein supply during gestation represents an environmental factor that affects physiological signaling pathways with long-term consequences for growth, function, and structure of various tissues. Hypothesizing that the offspring's transcriptome is persistently altered by maternal diets, we used a porcine model to monitor the longitudinal expression changes in muscle to identify pathways relevant to fetal initiation of postnatal growth and development. German Landrace gilts were fed isoenergetic gestational diets containing 6.5% (LP) or 12.1% protein. The longissimus dorsi samples were collected from offspring at 94 days postconception (dpc) and 1, 28, and 188 days postnatum (dpn) for expression profiling. At 94 dpc, 1 dpn, and 28 dpn relatively few transcripts (<130) showed an altered abundance between the dietary groups. In fact, at 94 dpc genes of G2/M checkpoint regulation and mitotic roles of Polo-like kinases showed lowered transcript abundance in LP. At 188 dpn 677 transcripts were altered including those related to oxidative phosphorylation, citrate cycle, fatty acid metabolism (higher abundance in LP) and cell cycle regulation (lower abundance in LP). Correspondingly, transcriptional alterations during pre and postnatal development differed considerably among dietary groups, particularly for genes related to cell cycle regulation (G1/S and G2/M checkpoint regulation; cyclines), growth factor signaling (GH, IGF1, mTOR, RAN, VEGF, INSR), lipid metabolism, energy metabolism, and nucleic acid metabolism. In skeletal muscle, fetal programming related to maternal LP diets disturbed gene expression in growth-related pathways into adulthood. Diet-dependent gene expression may hamper proper development, thereby affecting signaling pathways related to energy utilization.


Blood ◽  
1968 ◽  
Vol 31 (3) ◽  
pp. 292-303 ◽  
Author(s):  
YATARO YOSHIDA ◽  
AKIO TODO ◽  
SHIGERU SHIRAKAWA ◽  
GYOICHI WAKISAKA ◽  
HARUTO UCHINO

Abstract In order to elucidate the nature of the megaloblastic lesion at the cellular level, DNA, RNA, and protein synthesis was studied in megaloblasts of pernicious anemia. While microphotometric estimation of DNA content showed an increase in cells with DNA values ranging around the 4c value, autoradiographic studies with H3-thymidine indicated, rather, a decreased ability to synthesize DNA. Combined microphotometric and autoradiographic studies suggested the impaired DNA synthesis with occasional arrests of synthesis, as well as the prolongation of the S period with or without the prolongation of the G2 period. On the other hand, active incorporation of H3-uridine and H3-leucine indicated active or unaffected RNA and protein synthesis. Vitamin B12 treatment rapidly corrected these aberrant patterns of synthesis. The significance of these findings has been discussed in relation to the mechanism of megaloblastic hemopoiesis.


1962 ◽  
Vol 25 (2) ◽  
pp. 183-NP ◽  
Author(s):  
W. B. JOLLEY ◽  
W. E. MARTIN ◽  
J. W. BAMBERGER ◽  
L. W. STEARNS

SUMMARY Oestradiol-17β at a concentration of 3 × 10−3 m inhibits cleavage in sea urchin (Strongylocentrotus purpuratus) embryos. This inhibition is accompanied by a reduction in deoxyribonucleic acid (DNA) synthesis and little change in ribonucleic acid (RNA). The effects of oestradiol-17β upon the incorporation of glycine-1-14C and glycine-2-14C into the purines of DNA and RNA and the incorporation of glycine-2-14C into serine were studied. The incorporation of glycine-1-14C and glycine-2-14C into RNA was reduced, but the incorporation of glycine-2-14C into DNA was increased considerably over that of the controls. The incorporation of glycine-2-14C into serine was also accelerated by oestradiol. A possible explanation of the action of oestradiol-17β is offered. The moderate effect upon RNA is not surprising because there is little or no synthesis of this compound from the time of fertilization to blastulation under normal conditions.


Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1587 ◽  
Author(s):  
Gulsah Albayrak ◽  
Pinar Kilicarslan Sonmez ◽  
Damla Akogullari ◽  
Elgin Turkoz Uluer

Cyclophosphamide (CTX), also known as cytophosphane among other, is a medication used as chemotherapy and to suppress the immune system. The PI3K/AKT/mTOR pathway is involved in the regulation of diverse cellular functions, including cell growth, protein synthesis, cell cycle regulation, glucose metabolism, and motility. In our study eight weeks old C57BL/6 female mice were divided into 3 groups as control (C), sham (S) and experimental group. The experimental group has been established with CTX treatment. No treatment was applied to the C group. The S group were given an equal amount of saline. CTX was administered intraperitoneally one every 2 days for 3 weeks; the first dose was 70 mg/kg, the ongoing doses were 30 mg/kg. At the end of 3 weeks mice were sacrificed and kidneys were taken for investigation. In order to show the effect of cyclophosphamide in kidney tissue, the tissues were stained via indirect immunohistochemistry with PI3K, AKT and mTOR primary antibodies. In our study, PI3K, AKT and mTOR expression levels were found to be significantly decreased in CTX-mediated mechanisms indicating that the mechanisms of CTX might involve in the inhibition of PI3K/AKT/mTOR signaling pathway.


1993 ◽  
Vol 105 (1) ◽  
pp. 113-122 ◽  
Author(s):  
S. Adolph ◽  
S. Brusselbach ◽  
R. Muller

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.


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