Unstable β-globin mRNA in mRNA-deficient β0 thalassemia

Maquat, Lynne E.; Kinniburgh, Alan J.; Rachmilewitz, Eliezer A.; Ross, Jeffrey

doi:10.1016/0092-8674(81)90396-2

Cited by 267 publications

(205 citation statements)

References 44 publications

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“…In both prokaryotes and eukaryotes nonsense mutations in a gene can reduce the abundance of the mRNA transcribed from that gene (Morse and Yanofsky 1969;Losson and Lacroute 1979;Maquat et al 1981;Pelsy and Lacroute 1984;Baumann et al 1985;Nilsson et al 1987;Daar and Maquat 1988;Urlaub et al 1989;Cheng et al 1990;Gozalbo and Hohmann 1990;Barker and Beamon 1991;Gaspar et al 1991;Leeds et al 1991;Baserga and Benz 1992;Lim et al 1992;Cheng and Maquat 1993). Results of this study and others indicate that in S. cerevisiae this nonsense-mediated effect can be attributed to cytoplasmic events that are concurrent with mRNA translation.…”

Section: Nonsense Mutations Accelerate Cytoplasmic Mrna Decay In Yeastmentioning

confidence: 58%

mRNA destabilization triggered by premature translational termination depends on at least three cis-acting sequence elements and one trans-acting factor.

Peltz¹,

Brown²,

Jacobson³

1993

Genes Dev.

285

349

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Nonsense mutations in a gene can accelerate the decay rate of the mRNA transcribed from that gene, a phenomenon we describe as nonsense-mediated mRNA decay. Using amber (UAG) mutants of the yeast PGK1 gene as a model system, we find that nonsense-mediated mRNA decay is position dependent, that is, nonsense mutations within the initial two-thirds of the PGKl-coding region accelerate the decay rate of the PGK1 transcript ~<12-fold, whereas nonsense mutations within the carboxy-terminal third of the coding region have no effect on mRNA decay. Moreover, we find that this position effect reflects (1) a requirement for sequences 3' to the nonsense mutation that may be necessary for translational reinitiation or pausing, and (2) the presence of an additional sequence that, when translated, inactivates the nonsense-mediated mRNA decay pathway. This stabilizing element is positioned within the coding region such that it constitutes the boundary between nonsense mutations that do or do not affect mRNA decay. Rapid decay of PGK1 nonsense-containing transcripts is also dependent on the status of the UPF1 gene. Regardless of the position of an amber codon in the PGK1 gene, deletion of the UPF1 gene restores wild-type decay rates to nonsense-containing PGK1 transcripts.

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Section: Nonsense Mutations Accelerate Cytoplasmic Mrna Decay In Yeastmentioning

confidence: 58%

mRNA destabilization triggered by premature translational termination depends on at least three cis-acting sequence elements and one trans-acting factor.

Peltz¹,

Brown²,

Jacobson³

1993

Genes Dev.

285

349

View full text Add to dashboard Cite

show abstract

“…A role for translational efficiency in the regulation of mRNA stability is suggested by the destabilizing effects of drugs which disrupt mRNAribosome association (1,33), premature translational termination codons (41,45), and clustered rare codons (26). For all three types of effects it has been postulated that, when ribosome association is diminished or eliminated, mRNA degradation is enhanced by the increased access of specific nucleases to the mRNA.…”

Section: Discussionmentioning

confidence: 99%

“…It is likely that these complex decay kinetics reflect the sum of the decay rates of individual mRNAs (e.g., in D. discoideum, the most stable mRNAs have half-lives of approximately 10 h and the least stable mRNAs have half-lives which are approximately 10-fold shorter). It has been suggested that such large differences in the stability of individual mRNAs could be accounted for by differences in their respective sizes (39,52,58,63,78,81), poly(A) tail lengths (8,28,56,91), ribosome loading (1,26,33,41,45), or 5'-and 3'-untranslated (UT) sequences (42,53,64,69,74,76,89). To test the validity of these hypotheses, we have identified cloned cDNAs which encode mRNAs that are representative of the stability extremes in D. discoideum and have initiated a characterization of the properties of the respective mRNAs.…”

mentioning

confidence: 99%

Determinants of mRNA stability in Dictyostelium discoideum amoebae: differences in poly(A) tail length, ribosome loading, and mRNA size cannot account for the heterogeneity of mRNA decay rates.

Shapiro¹,

Herrick²,

Manrow³

et al. 1988

Mol. Cell. Biol.

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As an approach to understanding the structures and mechanisms which determine mRNA decay rates, we have cloned and begun to characterize cDNAs which encode mRNAs representative of the stability extremes in the poly(A)+ RNA population of Dictyostelium discoideum amoebae. The cDNA clones were identified in a screening procedure which was based on the occurrence of poly(A) shortening during mRNA aging. mRNA half-lives were determined by hybridization of poly(A)+ RNA, isolated from cells labeled in a 32P04 pulse-chase, to dots of excess cloned DNA. Individual mRNAs decayed with unique first-order decay rates ranging from 0.9 to 9.6 h, indicating that the complex decay kinetics of total poly(A)+ RNA in D. discoideum amoebae reflect the sum of the decay rates of individual mRNAs. Using specific probes derived from these cDNA clones, we have compared the sizes, extents of ribosome loading, and poly(A) tail lengths of stable, moderately stable, and unstable mRNAs. We found (i) no correlation between mRNA size and decay rate; (ii) no significant difference in the number of ribosomes per unit length of stable versus unstable mRNAs, and (iii) a general inverse relationship between mRNA decay rates and poly(A) tail lengths. Collectively, these observations indicate that mRNA decay in D. discoideum amoebae cannot be explained in terms of random nucleolytic events. The possibility that specific 3'-structural determinants can confer mRNA instability is suggested by a comparison of the labeling and turnover kinetics of different actin mRNAs. A correlation was observed between the steady-state percentage of a given mRNA found in polysomes and its degree of instability; i.e., unstable mRNAs were more efficiently recruited into polysomes than stable mRNAs. Since stable mRNAs are, on average, "older" than unstable mRNAs, this correlation may reflect a translational role for mRNA modifications that change in a time-dependent manner. Our previous studies have demonstrated both a time-dependent shortening and a possible translational role for the 3' poly(A) tracts of mRNA. We suggest, therefore, that the observed differences in the translational efficiency of stable and unstable mRNAs may, in part, be attributable to differences in steady-state poly(A) tail lengths.We have previously demonstrated that the mRNA population in vegetatively growing amoebae of the cellular slime mold Dictyostelium discoideum decays with complex kinetics, consisting of at least two major components: a rapidly decaying component with a half-life of approximately 50 min, and a long-lived component with a half-life of approximately 10 h (14, 58). Similar complex kinetics have been observed for the decay of poly(A)+ RNA in a variety of other eucaryotic cells (5,25,39,57,77,78,81). It is likely that these complex decay kinetics reflect the sum of the decay rates of individual mRNAs (e.g., in D. discoideum, the most stable mRNAs have half-lives of approximately 10 h and the least stable mRNAs have half-lives which are approximately 10-fold shorter). It has been s...

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“…The degradation rates a and b, and the asymptotic value c are calculated by the same least squares fitting procedure for each RNA. We calculated the half-life (T 1/2 ) using the following equation: Z(t) = [(cexp(-at) + (1-c)exp(-bt)) -0.5], 2 where Z(t) represents the squared value. When Z(t) is the minimum value, the half-life (T 1/2 ) nearly equal to t (hr).…”

Section: Acknowledgmentsmentioning

confidence: 99%

Identification of hundreds of novel UPF1 target transcripts by direct determination of whole transcriptome stability

et al. 2012

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Unstable β-globin mRNA in mRNA-deficient β0 thalassemia

Cited by 267 publications

References 44 publications

mRNA destabilization triggered by premature translational termination depends on at least three cis-acting sequence elements and one trans-acting factor.

mRNA destabilization triggered by premature translational termination depends on at least three cis-acting sequence elements and one trans-acting factor.

Determinants of mRNA stability in Dictyostelium discoideum amoebae: differences in poly(A) tail length, ribosome loading, and mRNA size cannot account for the heterogeneity of mRNA decay rates.

Identification of hundreds of novel UPF1 target transcripts by direct determination of whole transcriptome stability

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