Autoregulated instability of tubulin mRNAS: a novel eukaryotic regulatory mechanism

Cleveland, Don W.

doi:10.1016/0968-0004(88)90103-x

Cited by 154 publications

(94 citation statements)

References 21 publications

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“…15,1995 SEQUENCES REQUIRED FOR NONSENSE-MEDIATED mRNA DECAY 2239 ible mRNAs (68). The presence of this element correlates well with the rapid decay of these mRNAs.…”

Section: Discussionmentioning

confidence: 98%

“…Our results, as well as work from other laboratories, strongly indicate that the processes of mRNA turnover and translation are intimately linked and that understanding of this relationship is critical in elucidating the mechanism of mRNA decay (2, 5, 9, 11, 15, 21, 23, 29-31, 41, 53, 55-59, 76). The role of translation in determination of mRNA decay rates is direct, and, for certain instability elements identified in protein coding regions and 3Ј untranslated regions (3Ј-UTRs), translation of the protein coding region must occur in order for them to function (2,11,15,21,23,29,41,53,60,66,76).One clear example of the relationship between translation and mRNA decay is the observation that nonsense mutations in a gene can reduce the abundance of the mRNA transcribed from that gene in a process we term nonsense-mediated mRNA decay (55,56,58). Reduced mRNA levels or decreased stabilities of nonsense-containing transcripts have been observed in both prokaryotes and eukaryotes (6-8, 13, 14, 18, 20, 22, 42, 44-47, 51, 54, 56, 71, 75).…”

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Identification and Characterization of a Sequence Motif Involved in Nonsense-Mediated mRNA Decay

Zhang

Ruiz-Echevarría²,

Quan

et al. 1995

Molecular and Cellular Biology

123

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In both prokaryotes and eukaryotes, nonsense mutations in a gene can enhance the decay rate or reduce the abundance of the mRNA transcribed from that gene, and we call this process nonsense-mediated mRNA decay. We have been investigating the cis-acting sequences involved in this decay pathway. Previous experiments have demonstrated that, in addition to a nonsense codon, specific sequences 3 of a nonsense mutation, which have been defined as downstream elements, are required for mRNA destabilization. The results presented here identify a sequence motif (TGYYGATGYYYYY, where Y stands for either T or C) that can predict regions in genes that, when positioned 3 of a nonsense codon, promote rapid decay of its mRNA. Sequences harboring two copies of the motif from five regions in the PGK1, ADE3, and HIS4 genes were able to function as downstream elements. In addition, four copies of this motif can function as an independent downstream element. The sequences flanking the motif played a more significant role in modulating its activity when fewer copies of the sequence motif were present. Our results indicate the sequences 5 of the motif can modulate its activity by maintaining a certain distance between the sequence motif and the termination codon. We also suggest that the sequences 3 of the motif modulate the activity of the downstream element by forming RNA secondary structures. Consistent with this view, a stem-loop structure positioned 3 of the sequence motif can enhance the activity of the downstream element. This sequence motif is one of the few elements that have been identified that can predict regions in genes that can be involved in mRNA turnover. The role of these sequences in mRNA decay is discussed.The rates at which mRNAs decay play an important role in regulating gene expression. mRNA half-lives can vary from each other by as much as 100-fold (28,55,59,62,64), and this variation determines, in part, the cytoplasmic abundance of these RNAs. In addition, the decay rate of an mRNA can be modulated, and its half-life can vary depending on the cell type or the environmental situation of the cell (e.g., hormones, stress, cell cycle, etc. [3,55,62]). The goal of our work is to understand the cellular mechanisms that determine the stability of mRNAs.We are studying mRNA decay in the yeast Saccharomyces cerevisiae. Our results, as well as work from other laboratories, strongly indicate that the processes of mRNA turnover and translation are intimately linked and that understanding of this relationship is critical in elucidating the mechanism of mRNA decay (2, 5, 9, 11, 15, 21, 23, 29-31, 41, 53, 55-59, 76). The role of translation in determination of mRNA decay rates is direct, and, for certain instability elements identified in protein coding regions and 3Ј untranslated regions (3Ј-UTRs), translation of the protein coding region must occur in order for them to function (2,11,15,21,23,29,41,53,60,66,76).One clear example of the relationship between translation and mRNA decay is the observation that nonsense mutati...

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“…15,1995 SEQUENCES REQUIRED FOR NONSENSE-MEDIATED mRNA DECAY 2239 ible mRNAs (68). The presence of this element correlates well with the rapid decay of these mRNAs.…”

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Identification and Characterization of a Sequence Motif Involved in Nonsense-Mediated mRNA Decay

Zhang

Ruiz-Echevarría²,

Quan

et al. 1995

Molecular and Cellular Biology

123

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“…Although relatively little is known about the factors regulating microtubule assem- bly in higher plant cells, given the high degree of similarity between eukaryotic tubulins, it is likely that the assembly process will be similar to that observed in mammalian cells where the assembled microtubules have been shown to be in a dynamic equilibrium with a pool of soluble tubulin dimers (18). In cultured mammalian cells tubulin synthesis is autoregulated by a mechanism that is sensitive to the size of the soluble tubulin dimer pool (5). As a result, factors that stimulate or inhibit microtubule assembly change the amount of tubulin in the soluble tubulin dimer pool, and thereby alter the rate of tubulin synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…Where it has been examined, tubulin synthesis is regulated by a mechanism that is sensitive to changes in the amount of assembled microtubules. In cultured mammalian cells, tubulin synthesis is autoregulated by a post-transcriptional mechanism that is responsive to the size of the tubulin dimer pool (5). In other probe used in this study (14,15).…”

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confidence: 99%

Light Regulation of β-Tubulin Gene Expression during Internode Development in Soybean (Glycine max [L.] Merr.)

Bustos

Guiltinan²,

Cyr³

et al. 1989

Plant Physiol.

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The relationship between tubulin gene expression and cell elongation was explored in developing internodes of Glycine max (L.) Merr., using light as a variable to alter the rate of elongation. Illumination of 10-day-old etiolated seedlings not only stopped first internode elongation, but also brought about a 80% decrease in the steady state level of ,-tubulin mRNA over the course of the subsequent 12 hours. This strong down regulation of j6-tubulin mRNA occurred without significant changes in the size of the soluble tubulin pool and it was accompanied by a marked increase in chlorophyll a/b binding protein mRNA.cases, the tubulin dimer pool is maintained through both transcriptional and post-transcriptional control of tubulin gene expression (1,17). Little is known about the regulation of tubulin synthesis in plants, but Cyr et al. (8) observed changes of several fold in the levels of tubulin protein and mRNA during carrot somatic embryogenesis. Furthermore, Fukuda (11) reported that the rate of tubulin synthesis increased during the formation of cortical microtubules in differentiating tracheary elements. The involvement of cortical microtubules in cell elongation and the increase in tubulin levels and in microtubule assembly which has been shown to accompany cell elongation (9, 29), make elongating tissues attractive as systems for investigating the regulation oftubulin synthesis in higher plants. Here, we show that changes in ,Btubulin mRNA steady state levels and internode elongation rates vary concomitantly in light-grown and etiolated soybean seedlings. Internodes of etiolated seedlings exhibited elongation rates that were four to five fold greater than those observed in control seedlings grown under a 12 h light/dark cycle. The rapidly elongating internodes of dark-grown seedlings exhibited proportionally higher steady-state levels of jtubulin mRNA. Furthermore, subsequent illumination of the dark-grown seedlings brought about a reduction in the rate of elongation and a concomitant decrease in the steady-state level of #-tubulin mRNA.Microtubules are formed by the regulated self-assembly of the heterodimeric protein tubulin from a soluble tubulin dimer pool, and cytoplasmic microtubules are in a dynamic equilibrium with this tubulin dimer pool (18). Since microtubules can form and persist only when the tubulin dimer concentration exceeds a critical value, maintenance of the tubulin dimer pool at a level above this critical concentration is essential for microtubule formation. Where it has been examined, tubulin synthesis is regulated by a mechanism that is sensitive to changes in the amount of assembled microtubules. In cultured mammalian cells, tubulin synthesis is autoregulated by a post-transcriptional mechanism that is responsive to the size of the tubulin dimer pool (5).

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Lethal level overexpression of ?-tubulin in fission yeast causes mitotic arrest

Horio

Basaki

Takeoka

et al. 1999

Cell Motil. Cytoskeleton

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Autoregulated instability of tubulin mRNAS: a novel eukaryotic regulatory mechanism

Cited by 154 publications

References 21 publications

Identification and Characterization of a Sequence Motif Involved in Nonsense-Mediated mRNA Decay

Identification and Characterization of a Sequence Motif Involved in Nonsense-Mediated mRNA Decay

Light Regulation of β-Tubulin Gene Expression during Internode Development in Soybean (Glycine max [L.] Merr.)

Lethal level overexpression of ?-tubulin in fission yeast causes mitotic arrest

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