Should we kill the messenger? The role of the surveillance complex in translation termination and mRNA turnover

Czaplinski, Kevin; Ruiz-Echevarría, María J.; González, Caleb; Peltz, Stuart W.

doi:10.1002/(sici)1521-1878(199908)21:8<685::aid-bies8>3.0.co;2-4

Cited by 99 publications

(78 citation statements)

References 75 publications

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“…However, the decrease in mRNA may be due to instability as a result of arrested translation [34][35][36]. In order to probe this possibility, we studied the effects of puromycin on control, differentiating myoblasts and on TGF-β-treated, differentiationarrested myoblasts.…”

Section: Discussionmentioning

confidence: 99%

Regulation of calpain and calpastatin in differentiating myoblasts: mRNA levels, protein synthesis and stability

Barnoy

Supino-Rosin

Kosower

2000

Biochemical Journal

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Tel Aviv 69978, IsraelCalpain (Ca# + -dependent intracellular protease)-induced proteolysis has been considered to play a role in myoblast fusion to myotubes. We found previously that calpastatin (the endogenous inhibitor of calpain) diminishes transiently during myoblast differentiation. To gain information about the regulation of calpain and calpastatin in differentiating myoblasts, we evaluated the stability and synthesis of calpain and calpastatin, and measured their mRNA levels in L8 myoblasts. We show here that µ-calpain and m-calpain are stable, long-lived proteins in both dividing and differentiating L8 myoblasts. Calpain is synthesized in differentiating myoblasts, and calpain mRNA levels do not change during differentiation. In contrast, calpastatin (though also a long-lived protein in myoblasts), is less stable in differentiating myoblasts than in the dividing cells, and its synthesis is inhibited upon initiation of differentiation. Inhibition of cal-

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Section: Discussionmentioning

confidence: 99%

Regulation of calpain and calpastatin in differentiating myoblasts: mRNA levels, protein synthesis and stability

Barnoy

Supino-Rosin

Kosower

2000

Biochemical Journal

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“…Significant progress has been made in understanding how mRNA turnover is controlled in yeast. There are currently three known mRNA decay pathways in yeast, including the deadenylation-dependent decapping decay pathway, the 3Ј-to-5Ј exonucleolytic decay pathway, and the nonsense-mediated decay pathway (reviewed in Beelman and Parker, 1995;Decker, 1998;Czaplinski et al, 1999). Under normal conditions, the deadenylation-dependent decapping decay pathway appears to play the most significant role in degrading mRNAs in yeast.…”

Section: Introductionmentioning

confidence: 99%

The Target of Rapamycin Signaling Pathway Regulates mRNA Turnover in the YeastSaccharomyces cerevisiae

Albig

Decker

2001

MBoC

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The target of rapamycin (TOR) signaling pathway is an important mechanism by which cell growth is regulated by nutrient availability in eukaryotes. We provide evidence that the TOR signaling pathway controls mRNA turnover in Saccharomyces cerevisiae. During nutrient limitation (diauxic shift) or after treatment with rapamycin (a specific inhibitor of TOR), multiple mRNAs were destabilized, whereas the decay of other mRNAs was unaffected. Our findings suggest that the regulation of mRNA decay by the TOR pathway may play a significant role in controlling gene expression in response to nutrient depletion. The inhibition of the TOR pathway accelerated the major mRNA decay mechanism in yeast, the deadenylation-dependent decapping pathway. Of the destabilized mRNAs, two different responses to rapamycin were observed. Some mRNAs were destabilized rapidly, while others were affected only after prolonged exposure. Our data suggest that the mRNAs that respond rapidly are destabilized because they have short poly(A) tails prematurely either as a result of rapid deadenylation or reduced polyadenylation. In contrast, the mRNAs that respond slowly are destabilized by rapid decapping. In summary, the control of mRNA turnover by the TOR pathway is complex in that it specifically regulates the decay of some mRNAs and not others and that it appears to control decay by multiple mechanisms. INTRODUCTIONIt is estimated that most of the microorganisms in the environment exist in conditions in which nutrients are limiting (Lewis and Gattie, 1991). Nutrient availability is very important in controlling cell division, growth, and physiology in microorganisms as well as in multicellular organisms. One critical response in yeast to glucose limitation is the switch from fermentation to respiration, which is termed the diauxic shift. At the diauxic shift, major changes in gene expression are induced (reviewed in Werner-Washburne et al., 1996) including a general repression of translation (Fuge et al., 1994) and extensive changes in the abundance of mRNAs (DeRisi et al., 1997). The target of rapamycin (TOR) signaling pathway senses external nutrient availability and is involved in mediating the changes in gene expression induced at the diauxic shift (reviewed in Cutler et al., 1999;Dennis et al., 1999;Thomas and Hall 1999;Cardenas et al., 1999). Rapamycin artificially induces a starvation-like state in yeast (Barbet et al., 1996) by first forming a complex with the yeast FK506 binding protein, FKBP. This complex then binds to and represses the activity of the TOR1 and TOR2proteins (Heitman et al., 1991). The TOR signaling transduction pathway is conserved among yeast, flies, and mammals. In mammalian cells, the TOR protein homolog mTOR/ FRAP/RAFT1 also coordinates nutrient and mitogenic signals to control cell growth and cell-cycle progression (reviewed in Cutler et al., 1999;Thomas and Hall, 1999). The Drosophila TOR homolog dTOR also senses nutrient availability (Oldham et al., 2000;Zhang et al., 2000). The TOR proteins are protein kinases...

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“…In yeast, the major mRNA decay pathway involves a deadenylation-dependent decapping mechanism in which mRNA is initially deadenylated, then decapped by the Dcp1p decapping enzyme (1,2), and subsequently degraded by a highly processive 5Ј to 3Ј exoribonuclease (3,4). A deadenylation-independent mRNA turnover pathway has also been well characterized in yeast, whereby premature translation termination triggers decapping of the mRNA independent of the removal of the poly(A) tail (5)(6)(7). In an alternative decay pathway, the deadenylated mRNA is degraded by the exosome in a 3Ј to 5Ј direction (4,8,9).…”

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confidence: 99%

The hDcp2 protein is a mammalian mRNA decapping enzyme

Wang

Jiao

Carr-Schmid

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

312

367

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Decapping of mRNA is a critical step in eukaryotic mRNA turnover, yet the proteins involved in this activity remain elusive in mammals. We identified the human Dcp2 protein (hDcp2) as an enzyme containing intrinsic decapping activity. hDcp2 specifically hydrolyzed methylated capped RNA to release m 7 GDP; however, it did not function on the cap structure alone. hDcp2 is therefore functionally distinct from the recently identified mammalian scavenger decapping enzyme, DcpS. hDcp2-mediated decapping required a functional Nudix (nucleotide diphosphate linked to an X moiety) pyrophosphatase motif as mutations in conserved amino acids within this motif disrupted the decapping activity. hDcp2 is detected exclusively in the cytoplasm and predominantly cosediments with polysomes. Consistent with the localization of hDcp2, endogenous Dcp2-like decapping activity was detected in polysomal fractions prepared from mammalian cells. Similar to decapping in yeast, the presence of the poly(A) tail was inhibitory to the endogenous decapping activity, yet unlike yeast, competition of cap-binding proteins by cap analog did not influence the efficiency of decapping. Therefore the mammalian homologue of the yeast Dcp2 protein is an mRNA decapping enzyme demonstrated to contain intrinsic decapping activity.

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Should we kill the messenger? The role of the surveillance complex in translation termination and mRNA turnover

Cited by 99 publications

References 75 publications

Regulation of calpain and calpastatin in differentiating myoblasts: mRNA levels, protein synthesis and stability

Regulation of calpain and calpastatin in differentiating myoblasts: mRNA levels, protein synthesis and stability

The Target of Rapamycin Signaling Pathway Regulates mRNA Turnover in the YeastSaccharomyces cerevisiae

The hDcp2 protein is a mammalian mRNA decapping enzyme

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