Hormonal and Developmental Regulation of mRNA Turnover

Williams, David L.; Sensel, Martha G.; McTigue, Monica; Binder, Roberta

doi:10.1016/b978-0-08-091652-1.50012-8

Cited by 30 publications

(22 citation statements)

References 124 publications

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“…Also, after a severe heat shock, deadenylation occurs more rapidly in cells that have been preconditioned by a mild heat treatment than in cells that have not been preconditioned. There are only a few other known cases in which deadenylation is subject to such dynamic regulation (6,89).…”

Section: Discussionmentioning

confidence: 99%

Preferential deadenylation of Hsp70 mRNA plays a key role in regulating Hsp70 expression in Drosophila melanogaster.

1994

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Following a standard heat shock, -40%o ofHsp7O transcripts in Drosophila melanogaster lack a poly(A) tail. Since heat shock disrupts other aspects of RNA processing, this observation suggested that heat might disrupt polyadenylation as well. We find, however, that as the temperature is increased a larger fraction of Hsp7O RNA is polyadenylated. Poly(A)-deficient Hsp7O RNAs arise not from a failure in polyadenylation but from the rapid and selective removal of poly(A) from previously adenylated transcripts. Poly(A) removal is highly regulated: poly(A) is (i) removed much more rapidly from Hsp7O RNAs than from Hsp23 RNAs, (ii) removed more rapidly after mild heat shocks than after severe heat shocks, and (iii) removed more rapidly after a severe heat shock if cells have first been conditioned by a mild heat treatment. Poly(A) seems to be removed by simple deadenylation rather than by endonucleolytic cleavage 5' of the adenylation site. During recovery from heat shock, deadenylation is rapidly followed by degradation. In cells maintained at high temperatures, however, the two processes are uncoupled and Hsp7O RNAs are deadenylated without being degraded. These deadenylated mRNAs are translated with low efficiency. Deadenylation therefore allows Hsp7O synthesis to be repressed even when degradation of the mRNA is blocked. Poly(A) tail shortening appears to play a key role in regulating Hsp7O expression.The most abundant and tightly regulated heat-inducible protein in Drosophila melanogaster is Hsp7O (47,62). Hsp7O and its relatives make up a highly conserved protein family, with eukaryotic, eubacterial, and archaebacterial members sharing at least 50% amino acid identity (27,30,47). Eukaryotes have several Hsp7O proteins. Some are constitutive and are required for normal growth, whereas others are heat inducible and help organisms cope with the toxic effects of heat. In D. melanogaster the haploid genome encodes five virtually identical heat-inducible Hsp7O proteins (32), which share -70 to 80% amino acid identity with their constitutively expressed relatives (61, 64). Consistent with their independent patterns of regulation, the 3' and 5' sequences of the constitutive genes share little or no homology with those of the heat-inducible genes.The heat- strategies are used. First, the absence of introns in the Hsp7O gene (31) allows its transcripts to circumvent the high-temperature-induced block in mRNA splicing and move rapidly into the cytoplasm (91). Second, high temperatures block the turnover of the normally short-lived Hsp7O mRNA, allowing it to accumulate very rapidly to high concentrations (67). Third, the translation of normal cellular mRNAs is inhibited at high temperatures by mechanisms that act at the levels of both initiation and elongation (8,33,45,80). Hsp7O mRNAs are translated efficiently under these conditions because special sequences in their 5' untranslated leaders allow them to circumvent the block in translation (51; for a review, see reference 46).After return to normal temperatures, hsp synthe...

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Section: Discussionmentioning

confidence: 99%

Preferential deadenylation of Hsp70 mRNA plays a key role in regulating Hsp70 expression in Drosophila melanogaster.

1994

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“…Inhibition of protein synthesis has been shown to either increase or decrease the half-lives of many mRNAs (70). The inhibitors CHX, which blocks chain elongation (28,35,58), and puromycin, which causes premature chain termination (49,50,62), were used to determine the effects of inhibiting protein synthesis on apoll mRNA turnover in LMH/2A cells.…”

Section: Methodsmentioning

confidence: 99%

Reactivation of apolipoprotein II gene transcription by cycloheximide reveals two steps in the deactivation of estrogen receptor-mediated transcription.

et al. 1994

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In this report, we describe apolipoprotein II (apoll) gene expression in cell lines derived by stable expression of the chicken estrogen receptor in LMH chicken hepatoma cells. In cell lines expressing high levels of receptor (LMH/2A), apoll gene expression is increased by estrogen 300-fold compared with levels in the receptordeficient parent LMH line. LMH/2A cells show apoll mRNA induction and turnover kinetics similar to those in chicken liver. Inhibition of protein synthesis with cycloheximide (CHX) or puromycin following estrogen withdrawal superinduces apoll mRNA without affecting apoll mRNA stability. Superinduction is due to an estrogen-independent reactivation of apoll gene transcription. The apoll gene can be reactivated by CHX for up to 24 h following hormone withdrawal, suggesting that the gene is in a repressed yet transcriptionally competent state. These results reveal two distinct events necessary for termination of estrogen receptormediated transcription. The first event, removal of hormone, is sufficient to stop transcription when translation is ongoing. The second event is revealed by the CHX-induced superinduction of apoll mRNA following hormone withdrawal. This superinduction suggests that deactivation of estrogen receptor-mediated transcription requires a labile protein. Furthermore, reactivation of apoll gene expression by CHX and estrogen is additive, suggesting that estrogen is unable to overcome repression completely. Thus, a labile protein may act to repress estrogen receptor-mediated transcription of the apoll gene.In avian liver, estrogens regulate the expression of a number of egg yolk precursor proteins required for the transport of nutrients to the developing oocyte (5). Among the proteins regulated by estrogen are vitellogenin I (VTGI), VTGII, and VTGIII (63, 64), apolipoprotein B (apoB) (17) and apoll (18) of very low density lipoprotein, and riboflavin-and biotinbinding proteins (16,66). The primary action of estrogen is to increase transcription of the genes encoding these proteins via binding to the estrogen receptor. In addition to regulating transcription, estrogen also alters the cytoplasmic stability of apoll and VTGII mRNAs (30,71). Analysis of the mechanisms of transcriptional regulation of these genes as well as the study of mRNA turnover in avian liver cells has been hampered by the absence of a suitable homologous cell line. Studies of gene activation and estrogen-dependent alterations in chromatin structure and DNA methylation patterns have been restricted to animal studies or tissue homogenates (2,3,14,15,38,42,67,68

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“…Several hormonal and developmental signals have been shown to modulate gene expression by altering mRNA stability or mRNA degradation (1). Post-transcriptional regulation of mRNA expression has been shown to play an important role in controlling the level of rapidly induced mRNAs.…”

mentioning

confidence: 99%

Accumulation of Sequence-specific RNA-binding Proteins in the Cytosol of Activated T Cells Undergoing RNA Degradation and Apoptosis

Mondino

Jenkins

1995

Journal of Biological Chemistry

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Hormonal and Developmental Regulation of mRNA Turnover

Cited by 30 publications

References 124 publications

Preferential deadenylation of Hsp70 mRNA plays a key role in regulating Hsp70 expression in Drosophila melanogaster.

Preferential deadenylation of Hsp70 mRNA plays a key role in regulating Hsp70 expression in Drosophila melanogaster.

Reactivation of apolipoprotein II gene transcription by cycloheximide reveals two steps in the deactivation of estrogen receptor-mediated transcription.

Accumulation of Sequence-specific RNA-binding Proteins in the Cytosol of Activated T Cells Undergoing RNA Degradation and Apoptosis

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