As obligate intracellular parasites, viruses expertly modify cellular processes to facilitate their replication and spread, often by encoding genes that mimic the functions of cellular proteins while ...lacking regulatory features that modify their activity. We show that the human cytomegalovirus UL97 protein has activities similar to cellular cyclin-cyclin-dependent kinase (CDK) complexes. UL97 phosphorylated and inactivated the retinoblastoma tumor suppressor, stimulated cell cycle progression in mammalian cells, and rescued proliferation of Saccharomyces cerevisiae lacking CDK activity. UL97 is not inhibited by the CDK inhibitor p21 and lacks amino acid residues conserved in the CDKs that permit the attenuation of kinase activity. Thus, UL97 represents a functional ortholog of cellular CDKs that is immune from normal CDK control mechanisms.
IBMM of OH adsorbates and interphases on Si-based materials Herbots, N.; Xing, Qian; Hart, M. ...
Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms,
02/2012, Letnik:
272
Journal Article
Recenzirano
Using ion beam modification, films composed of synthesized “interphases” of ordered silica on OH-passivated (1
×
1)Si(100) underwent surface electro-chemical changes quantified by surface free energy ...via Sessile drop method and contact angle analysis using Young’s equation and Van Oss theory. IBMM caused the surface free energies initially ranging from 26.0
mJ/m
2 to 57.3
mJ/m
2 to converge to 43.1–45.4
mJ/m
2 for various passivated and as-received wafer samples alike. Although TMAFM also identified topographic changes, these changes did not correlate to the change of surface free energies. Ion beam modification of the ordered silica film on Si(100) surface is analyzed using 3.045
MeV
16O(α, α)
16O nuclear resonance scattering (NRS) in conjunction with channeling in 〈1
1
1〉 direction, which demonstrated the convergence of the partially ordered oxygen to amorphous at about 55
μC/mm
2 He
++ flux. Additionally, Si surface peak channeling in 〈1
0
0〉 and 〈1
1
1〉 directions also experienced an uptrend in areal density as incident ion flux increased, while the rotating random Si signal height remains stable, showing a disruption in the surface order during IBMM.
mRNA decay rates often increase when translation is terminated prematurely due to a frameshift or nonsense mutation. We have identified a yeast gene, UPF1, that codes for a trans-acting factor whose ...function is necessary for enhanced turnover of mRNAs containing a premature stop codon. In the absence of UPF1 function, frameshift or nonsense mutations in the HIS4 or LEU2 genes that normally cause rapid mRNA decay fail to have this effect. Instead, the mRNAs decay at rates similar to the corresponding wild-type mRNAs. The stabilization of frameshift or nonsense mRNAs observed in upf1- strains does not appear to result from enhanced readthrough of the termination signal. Loss of UPF1 function has no effect on the accumulation or stability of HIS4+ or LEU2+ mRNA, suggesting that the UPF1 product functions only in response to a premature termination signal. When we examined the accumulation and stability of other wild-type mRNAs in the presence or absence of UPF1, including MAT alpha 1, STE3, ACT1, PGK1, PAB1, and URA3 mRNAs, only the URA3 transcript was affected. On the basis of these and other results, the UPF1 product appears to participate in a previously uncharacterized pathway leading to the degradation of a limited class of yeast transcripts.
In Saccharomyces cerevisiae, nonsense-mediated mRNA decay (NMD) requires Upf1p, Upf2p, and Upf3p to accelerate the decay rate of two unique classes of transcripts: (1) nonsense mRNAs that arise ...through errors in gene expression, and (2) naturally occurring transcripts that lack coding errors but have built-in features that target them for accelerated decay (error-free mRNAs). NMD can trigger decay during any round of translation and can target Cbc-bound or eIF-4E-bound transcripts. Extremely low concentrations of the Upf proteins relative to the total pool of transcripts make it difficult to understand how nonsense transcripts are selectively recruited. To stimulate debate, we propose two alternative mechanisms for selecting nonsense transcripts for NMD and for assembling components of the surveillance complex, one for the first (pioneer) round of translation, called "nuclear marking," and the other for subsequent rounds, called "reverse assembly." The model is designed to accommodate (1) the low abundance of NMD factors, (2) the role of nucleocytoplasmic shuttling proteins in NMD, (3) the independent and nonobligate order of assembly of two different subcomplexes of NMD factors, and (4) the ability of NMD to simultaneously reduce or eliminate the synthesis of truncated proteins produced by nonsense transcripts while down-regulating but not completely eliminating functional proteins produced from error-free NMD-sensitive transcripts
The Saccharomyces cerevisiae SEN1 gene codes for a nuclear-localized superfamily I helicase. SEN1 is an ortholog of human SETX (senataxin), which has been implicated in the neurological disorders ...ataxia-ocular apraxia type 2 and juvenile amyotrophic lateral sclerosis. Pleiotropic phenotypes conferred by sen1 mutations suggest that Sen1p affects multiple steps in gene expression. Sen1p is embedded in a protein-protein interaction network involving direct binding to multiple partners. To test whether the interactions occur independently or in a dependent sequence, we examined interactions with the RNA polymerase II subunit Rpb1p, which is required for transcription, and Rnt1p, which is required for 3'-end maturation of many noncoding RNAs. Mutations were identified that impair one of the two interactions without impairing the other interaction. The effects of the mutants on the synthesis of U5 small nuclear RNA were analyzed. Two defects were observed, one in transcription termination and one in 3'-end maturation. Impairment of the Sen1p-Rpb1p interaction resulted in a termination defect. Impairment of the Sen1p-Rnt1p interaction resulted in a processing defect. The results suggest that the Sen1p-Rpb1p and Sen1p-Rnt1p interactions occur independently of each other and serve genetically separable purposes in targeting Sen1p to function in two temporally overlapping steps in gene expression.