UV-Induced stabilization of c-fos and other short-lived mRNAs.
Christine Blattner,P. Kannouche,Margarethe Litfin,Klaus Bender,Hans J. Rahmsdorf,Jaime F. Angulo,Peter Herrlich +6 more
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TLDR
The data indicate that the signal flow induced by UV radiation addresses not only protein stability and transcription but also RNA stability, a hitherto-unrecognized level of UV-induced regulation.Abstract:
Irradiation of cells with short-wavelength ultraviolet light (UVC) changes the program of gene expression, in part within less than 15 min. As one of the immediate-early genes in response to UV, expression of the oncogene c-fos is upregulated. This immediate induction is regulated at the transcriptional level and is transient in character, due to the autocatalyzed shutoff of transcription and the rapid turnover of c-fos mRNA. In an experiment analyzing the kinetics of c-fos mRNA expression in murine fibroblasts irradiated with UVC, we found that, in addition to the initial transient induction, c-fos mRNA accumulated in a second wave starting at 4 to 5 h after irradiation, reaching a maximum at 8 h, and persisting for several more hours. It was accompanied by an increase in Fos protein synthesis. The second peak of c-fos RNA was caused by an UV dose-dependent increase in mRNA half-life from about 10 to 60 min. With similar kinetics, the mRNAs of other UV target genes (i.e., the Kin17 gene, c-jun, IkappaB, and c-myc) were stabilized (e.g., Kin17 RNA from 80 min to more than 8 h). The delayed response was not due to autocrine cytokine secretion with subsequent autostimulation of the secreting cells or to UV-induced growth factor receptor activation. Cells unable to repair UVC-induced DNA damage responded to lower doses of UVC with an even greater accumulation of c-fos and Kin17 mRNAs than repair-proficient wild-type cells, suggesting that a process in which a repair protein is involved regulates mRNA stability. Although resembling the induction of p53, a DNA damage-dependent increase in p53 was not a necessary intermediate in the stabilization reaction, since cells derived from p53 knockout mice showed the same pattern of c-fos and Kin17 mRNA accumulation as wild-type cells. The data indicate that the signal flow induced by UV radiation addresses not only protein stability (p53) and transcription but also RNA stability, a hitherto-unrecognized level of UV-induced regulation.read more
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Genome-wide analysis of long noncoding RNA stability
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Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals
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TL;DR: This study determined the half-lives of 11,052 mRNAs and 1418 ncRNAs in HeLa Tet-off (TO) cells by developing a novel genome-wide method, which was named 5'-bromo-uridine immunoprecipitation chase-deep sequencing analysis (BRIC-seq), and identified and characterized several novel long nCRNAs involved in cell proliferation from the group of short-lived nc RNAs.
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Mathematical model of NF- κB regulatory module
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The major mRNA‐associated protein YB‐1 is a potent 5′ cap‐dependent mRNA stabilizer
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TL;DR: Data support a model whereby down‐regulation of eIF4E activity or increasing the YB‐1 mRNA binding activity or concentration in cells activates a general default pathway for mRNA stabilization.
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Lawrence A. Donehower,Michele Harvey,Betty L. Slagle,Mark J. McArthur,Charles A. Montgomery,Janet S. Butel,Allan Bradley +6 more
TL;DR: Observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.
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Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family
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AU-rich elements: characterization and importance in mRNA degradation.
Chyi-Ying A. Chen,Ann-Bin Shyu +1 more
TL;DR: Observations suggest that Adenylate/uridylate-rich elements play a critical role in the regulation of gene expression during cell growth and differentiation and in the immune response.
Journal ArticleDOI
Ultraviolet Light and Osmotic Stress: Activation of the JNK Cascade Through Multiple Growth Factor and Cytokine Receptors
Caridad Rosette,Michael Karin +1 more
TL;DR: Whereas activation of each receptor alone resulted in modest activation of JNK, coadministration of EGF, IL-1, and TNF resulted in a strong synergistic response equal to that caused by exposure to osmotic shock or UV light, inhibition of clustering or receptor down-regulation attenuated both the osmosis shock and UV responses.
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