Interplay between Transcription and RNA Degradation

Yamada, Toshimichi; Nagahama, Masami; Akimitsu, Nobuyoshi

doi:10.5772/intechopen.71862

Cited by 4 publications

(3 citation statements)

References 85 publications

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“…These results suggested that SOX2 negatively regulated FOXO1 at the mRNA degradation level. The degradation of mRNA can be controlled by cis-acting sequence elements or trans-acting factors [ 19 ]. Some RNA-binding proteins, such as HUR, Nucleolin (NCL), and AUF1, have been reported to bind to their target mRNAs and regulate mRNA stability [ 20 , 21 , 22 ].…”

Section: Resultsmentioning

confidence: 99%

SOX2 Promotes Invasion in Human Bladder Cancers through MMP2 Upregulation and FOXO1 Downregulation

Xie

Hua

Huang

et al. 2022

IJMS

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SOX2, a member of the SRY-related HMG-box (SOX) family, is abnormally expressed in many tumors and associated with cancer stem cell-like properties. Previous reports have shown that SOX2 is a biomarker for cancer stem cells in human bladder cancer (BC), and our most recent study has indicated that the inhibition of SOX2 by anticancer compound ChlA-F attenuates human BC cell invasion. We now investigated the mechanisms through which SOX2 promotes the invasive ability of BC cells. Our studies revealed that SOX2 promoted SKP2 transcription and increased SKP2-accelerated Sp1 protein degradation. As Sp1 is a transcriptionally regulated gene, HUR transcription was thereby attenuated, and, in the absence of HUR, FOXO1 mRNA was degraded fast, which promoted BC cell invasion. In addition, SOX2 promoted BC invasion through the upregulation of nucleolin transcription, which resulted in increased MMP2 mRNA stability and expression. Collectively, our findings show that SOX2 promotes BC invasion through both SKP2-Sp1-HUR-FOXO1 and nucleolin-MMP2 dual axes.

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Section: Resultsmentioning

confidence: 99%

SOX2 Promotes Invasion in Human Bladder Cancers through MMP2 Upregulation and FOXO1 Downregulation

Xie

Hua

Huang

et al. 2022

IJMS

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“…These results suggest that some peptide mRNA could be rapidly expressed after the stimuli as immediate early genes do. Generally, the amount of mRNA in the cell depends on both the rates of mRNA transcription in the nucleus and mRNA degradation in the cytoplasm [ 58 ]. Thus, the rapid increase in the AVPV/PeN Kiss1 mRNA expression in the current study would be the results of an increase in transcription and/or decrease in degradation of the Kiss1 mRNA.…”

Section: Discussionmentioning

confidence: 99%

Mating-induced increase in <i>Kiss1</i> mRNA expression in the anteroventral periventricular nucleus prior to an increase in LH and testosterone release in male rats

Watanabe

Ikegami

Nakamura

et al. 2020

Journal of Reproduction and Development

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Kisspeptin has an indispensable role in gonadotropin-releasing hormone/gonadotropin secretion in mammals. In rodents, kisspeptin neurons are located in distinct brain regions, namely the anteroventral periventricular nucleus-periventricular nucleus continuum (AVPV/PeN), arcuate nucleus (ARC), and medial amygdala (MeA). Among them, the physiological role of AVPV/PeN kisspeptin neurons in males has not been clarified yet. The present study aims to investigate the acute effects of the olfactory and/or mating stimulus with a female rat on hypothalamic and MeA Kiss1 mRNA expression, plasma luteinizing hormone (LH) and testosterone levels in male rats. Intact male rats were exposed to the following stimuli: exposure to clean bedding; exposure to female-soiled bedding as a female-olfactory stimulus; exposure to female-soiled bedding and mating stimulus with a female rat. The mating stimulus significantly increased the number of the AVPV/PeN Kiss1 mRNA-expressing cells in males within 5 minutes after the exposure, and significantly increased LH and testosterone levels, followed by an increase in male sexual behavior. Whereas, the males exposed to female-soiled bedding showed a moderate increase in LH levels and no significant change in testosterone levels and the number of the AVPV/PeN Kiss1 mRNA-expressing cells. Importantly, none of the stimuli affected the number of Kiss1 mRNA-expressing cells in the ARC and MeA. These results suggest that the mating-induced increase in AVPV/PeN Kiss1 mRNA expression may be, at least partly, involved in stimulating LH and testosterone release, and might consequently ensure male mating behavior. This study would be the first report suggesting that the AVPV/PeN kisspeptin neurons in males may play a physiological role in ensuring male reproductive performance.

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“…5. RNA degradation may in reality be more complex than modeled here, with ribonuclease fluctuations [46], multi-step degradation [47], sequence-dependent degradation [48,49], and transcription-coupled degradation [50] potentially yielding deviations from simple Poisson process degradation. Our simulation-based platform can address these effects analogously to elongation.…”

mentioning

confidence: 99%

Stochastic simulation and statistical inference platform for visualization and estimation of transcriptional kinetics

et al. 2020

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Recent advances in single-molecule fluorescent imaging have enabled quantitative measurements of transcription at a single gene copy, yet an accurate understanding of transcriptional kinetics is still lacking due to the difficulty of solving detailed biophysical models. Here we introduce a stochastic simulation and statistical inference platform for modeling detailed transcriptional kinetics in prokaryotic systems, which has not been solved analytically. The model includes stochastic two-state gene activation, mRNA synthesis initiation and stepwise elongation, release to the cytoplasm, and stepwise co-transcriptional degradation. Using the Gillespie algorithm, the platform simulates nascent and mature mRNA kinetics of a single gene copy and predicts fluorescent signals measurable by time-lapse single-cell mRNA imaging, for different experimental conditions. To approach the inverse problem of estimating the kinetic parameters of the model from experimental data, we develop a heuristic optimization method based on the genetic algorithm and the empirical distribution of mRNA generated by simulation. As a demonstration, we show that the optimization algorithm can successfully recover the transcriptional kinetics of simulated and experimental gene expression data. The platform is available as a MATLAB software package at https:// data.caltech.

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Interplay between Transcription and RNA Degradation

Cited by 4 publications

References 85 publications

SOX2 Promotes Invasion in Human Bladder Cancers through MMP2 Upregulation and FOXO1 Downregulation

SOX2 Promotes Invasion in Human Bladder Cancers through MMP2 Upregulation and FOXO1 Downregulation

Mating-induced increase in <i>Kiss1</i> mRNA expression in the anteroventral periventricular nucleus prior to an increase in LH and testosterone release in male rats

Stochastic simulation and statistical inference platform for visualization and estimation of transcriptional kinetics

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