ABSTRACT
Transcription is a multi-stage process that coordinates several steps during the transcription cycle including pre-initiation,initiation and elongation.Recent advances by genome-wide study suggest that control of transcription elongation is a critical step for precise regulation of gene expression across species from Drosophila to mammals.Here we review the molecular mechanisms of how transcription elongation of RNA polymeraseⅡ(PolⅡ) is modulated by the major pausing factors-NELF,DSIF and the positive elongation factor P-TEFb,which is the key player in pause release.We also discuss the potential implications of regulation of transcription elongation in pathogenesis of cancer,inflammation and virus infection.
ABSTRACT
Objective: To establish a rapid high-throughput screening model with positvive transcription elongation factor (p-TEFb) as target for screening the inhibitors of HIV. Methods: Double cross plasmid of BD-Tat and AD-CyclinT1 was established and transformed into yeast AH109 and Y187, respectively. AH109/pGBKT7-Tat was mated with Y187/pGADT7-CyclinT1 and the diploids were subjected to autoactivation, toxicity test, and reporter gene assay. The screening model based on double hybrid system was established. Results: Two out of 20 kinds of Chinese materia medica possessing immunity-enhancing effects were identified as primary hits, the anti-HIV activity of these two positive drugs was already demonstrated by other researchers through detecting the suppression effects on HIV duplication in vitro. Conclusion: The system established in this paper can be used for rapid high-throughput screening anti-HIV chemicals or herbs. Further research for the obtained two positive Chinese materia medica, Cibotii Rhizoma and Coptidis Rhizom should be carried out to isolate the effective component for disrupting the interaction between HIV Tat and CyclinT1.
ABSTRACT
AIM To inVestigate the positiVe transcription elongation factor b(P-TEFb)expressjon and the effect of berberine on diabetic retina of the rat.METHODS Type 2 diabetes mellitus rat models were diabetic control rats(group A)that neither received STZ nor the high-carbohydrate/high-fat diet;16-wk diabetic rats without any drug treatment(group B);diabetic rats treated with berberine at a dose of 75,150 or staining and P-TEFb(cyclin-dependent kinases 9(CDK9)and cyclin T1)protein expression was detected by immunohistochemjstry.RESULTS The retinas of control group were thicker than those of other 6 groups.After thickness but no difference in retinal structure among all groups.Middle-.high-dose berberine and rosiglitazone fenofibrate showed no effect on CDK9 and cyclin T1 expression.CONCLUSION Berberine modulating P-TEFb level in diabetic retina may probably be one of the mechanisms to ameliorate retinopatby induced by STZ and the high-carbohydrate/high-fat diet.