Divergence towards a dead end? Cleavage of the divergent domains of ribosomal RNA in apoptosis

Houge, Gunnar; Døskeland, Stein Ove

doi:10.1007/bf01920105

Cited by 39 publications

(34 citation statements)

References 30 publications

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“…Furthermore, the exceptional integrity of 28S rRNA in apoptotic HL-60 cells alludes that these cells lack a molecular mechanism for apoptotic 28S rRNA cleavage. Interestingly, the absence of both primary D2 and primary D8 cleavage indicates that the two apoptotic cleavage pathways are interconnected (see Houge and Dùskeland, 1996, for a more detailed discussion of the two different options for 28S rRNA cleavage in apoptosis). In rat myeloid IPC-81 cells, apoptotic D8 cleavage occurred in an exposed area of the ribosomal rRNA, while D2 cleavage was found in stem-loop junctions inaccessible to chemical agents capable of modifying single-stranded bases in the rRNA molecule (Leffers and Anderson, 1993;Holmberg et al, 1994;Houge et al, 1995).…”

Section: Resultsmentioning

confidence: 99%

The ability to cleave 28S ribosomal RNA during apoptosis is a cell-type dependent trait unrelated to DNA fragmentation

et al. 1997

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Discrete cleavages within 28S rRNA divergent domains have previously been found to coincide with DNA fragmentation during apoptosis. Here we show that rRNA and DNA cleavages can occur independently in apoptotic cells, i.e. that the previously observed correlation is likely to be coincidental. In HL-60 cells, apoptosis with massive DNA fragmentation could be induced without any signs of rRNA cleavage. The opposite situation; rRNA cleavage without concomitant internucleosomal DNA fragmentation, was found in okadaic acid-treated Molt-4 cells. Other leukemia cell lines underwent apoptosis either without (K562 and Molt-3) or with (U937) both forms of polynucleotide cleavage. In K562 cells transfected with a temperature-sensitive p53 mutant, internucleosomal DNA fragmentation but not 28S rRNA cleavage was inducible by wild-type p53 expression. The absence of apoptotic rRNA cleavage in some cell types suggests that this phenomenon is tightly regulated and unrelated to DNA fragmentation or a presumed scheme for general macromolecular degradation in apoptotic cells.

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Section: Resultsmentioning

confidence: 99%

The ability to cleave 28S ribosomal RNA during apoptosis is a cell-type dependent trait unrelated to DNA fragmentation

et al. 1997

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“…1,2 Apoptotic cells are recognized by cell shrinkage, cell surface budding and chromatin hypercondensation. Specific cleavage of DNA, 2 RNA, 3 and`flipping' of phospholipids to the external face of the cell membrane 4,5 are also commonly associated with apoptosis. Caspases are believed to be instrumental in the execution of regulated death.…”

Section: Introductionmentioning

confidence: 99%

Ultrarapid caspase-3 dependent apoptosis induction by serine/threonine phosphatase inhibitors

et al. 1999

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The protein phosphatase (PP) inhibitors nodularin and microcystin-LR induced apoptosis with unprecedented rapidity, more than 50% of primary hepatocytes showing extensive surface budding and shrinkage of cytoplasm and nucleoplasm within 2 min. The apoptosis was retarded by the general caspase inhibitor Z-VAD.fmk. To circumvent the inefficient uptake of microcystin and nodularin into nonhepatocytes, toxins were microinjected into 293 cells, Swiss 3T3 fibroblasts, promyelocytic IPC-81 cells, and NRK cells. All cells started to undergo budding typical of apoptosis within 0.5 ± 3 min after injection. This was accompanied by cytoplasmic and nuclear shrinkage and externalization of phosphatidylserine. Overexpression of Bcl-2 did not delay apoptosis. Apoptosis induction was slower and Z-VAD.fmk independent in caspase-3 deficient MCF-7 cells. MCF-7 cells stably transfected with caspase-3 showed a more rapid and Z-VAD.fmk dependent apoptotic response to nodularin. Rapid apoptosis induction required inhibition of both PP1 and PP2A, and the apoptosis was preceded by increased phosphorylation of several proteins, including myosin light chain. The protein phosphorylation occurred even in the presence of apoptosis-blocking concentrations of Z-VAD.fmk, indicating that it occurred upstream of caspase activation. It is suggested that phosphatase-inhibiting toxins can induce caspase-3 dependent apoptosis in an ultrarapid manner by altering protein phosphorylation.

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“…56,57 D domains have therefore been suggested to be involved in the translational machinery as riboregulators, protein anchoring regions, or as domains for RNA-RNA interactions. 58 In 1993, 17 years after the discovery that chromosomal DNA is cleaved during apoptosis, 28 Houge and co-workers observed that in apoptotic rat myeloid leukemia IPC-81 cells the 28S rRNA molecule, which is a component of the 60S large ribosomal subunit, was cleaved into several distinct fragments. 59 Cleavage of 28S rRNA was first observed between 2 and 4 h after the induction of apoptosis and correlated with an increase in the percentage of morphologically changed (apoptotic) cells.…”

Section: The 28s Rrna Molecule Is Cleaved During Apoptosismentioning

confidence: 99%

“…61 Based on the speculation that the primary target that is cleaved in the 28S rRNA molecule can either be in the D2 or in the D8 domain, it was hypothesized that there might be two alternative apoptotic cleavage pathways. 58 In pathway 1, apoptotic cleavage starts in D8b and is subsequently followed by a secondary cleavage in D2c. Pathway 2 is characterized by an initial cleavage 5' upstream of the D2c subdomain followed by a 3' cleavage downstream of the D2c subdomain which results in the excision of D2c.…”

Section: The 28s Rrna Molecule Is Cleaved During Apoptosismentioning

confidence: 99%

“…Pathway 2 is characterized by an initial cleavage 5' upstream of the D2c subdomain followed by a 3' cleavage downstream of the D2c subdomain which results in the excision of D2c. 58 In apoptotic bovine endothelial cells the alternative targets for rRNA cleavage are the D6 and D8 domains. 61 Cleavage in D8 is speculated to be mediated by an RNase activity that is activated during apoptosis because D8 is, in comparison to D2 and D6, more sensitive to the incubation with RNase T 1 and RNase U 2 .…”

Section: The 28s Rrna Molecule Is Cleaved During Apoptosismentioning

confidence: 99%

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Caspase-dependent cleavage of nucleic acids

et al. 2000

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Autoimmune diseases are frequently characterized by the presence of autoantibodies directed against nucleic acidprotein complexes present in the nucleus of the cell. The mechanisms by which these autoantigenic molecules escape immunological tolerance are largely unknown, although a number of recent observations suggest that modified selfproteins generated during apoptosis may play an important role in the development of autoimmunity. It has been hypothesized that the recognition of these modified selfproteins by the immune system may promote autoantibody production. While apoptosis is specifically characterized by posttranslational modification of proteins, recent findings also show that nucleic acids are modified. This review summarizes the specific cleavages of some of these key nucleic acids, i.e. chromosomal DNA, ribosomal RNA and small structural RNAs (U1 snRNA, Y RNA), in apoptotic cells.

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Divergence towards a dead end? Cleavage of the divergent domains of ribosomal RNA in apoptosis

Cited by 39 publications

References 30 publications

The ability to cleave 28S ribosomal RNA during apoptosis is a cell-type dependent trait unrelated to DNA fragmentation

The ability to cleave 28S ribosomal RNA during apoptosis is a cell-type dependent trait unrelated to DNA fragmentation

Ultrarapid caspase-3 dependent apoptosis induction by serine/threonine phosphatase inhibitors

Caspase-dependent cleavage of nucleic acids

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