Publication: Changes in extranucleolar transcription
during actinomycin D-induced apoptosis
Authors
Fraschini, A. ; Bottone, M.G. ; Scovassi, A.I. ; Denegri, M. ; Risueño, M.C. ; Testillano, P.S. ; Martin, T.E. ; Biggiogera, M. ; Pellicciari, C.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Actinomycin D (AMD) inhibits DNAdependent
RNA polymerases and its selectivity depends
on the concentration used; at very high concentrations it
may also induce apoptosis. This study investigates the
effects of different concentrations (0.01 to 1 µg/ml) of
AMD on RNA transcription and maturation and on the
organization of nuclear ribonucleoproteins (RNPs), and
their relationship with apoptosis induction. Human HeLa
cells were used as a model system. At the lowest
concentration used, AMD induced the segregation of the
nucleolar components and impaired r-RNA synthesis, as
revealed by the decreased immunopositivity for bromouridine
incorporation and for DNA/RNA hybrid
molecules. The synthesis of pre-mRNAs, on the
contrary, was active, while the immunolabeling of
snRNP proteins and of the SC-35 splicing factor strongly
decreased on perichromatin fibrils (where they are
involved in co-transcriptional splicing). This suggests
that the post-transcriptional maturation of extranucleolar
RNAs was also affected. Moreover, still in the absence
of typical late morphological or biochemical signs of
apoptosis (i.e. chromatin condensation), these cells
displayed the early apoptotic features, i.e. the
externalization of phosphatidylserine residues on the
plasma membrane and propidium iodide exclusion in
vivo. At the highest concentrations of AMD used,
apoptosis massively occurred, with the typical
morphological events (progressive chromatin
condensation, clustering of snRNPs and SC-35 splicing
factor, cell blebbing). However, transcription of hnRNAs
was maintained in the residual areas of diffuse chromatin
up to advanced apoptotic stages. The inhibition of rRNA
synthesis and the defective pre-mRNA maturation seem
to be part of the apoptotic process induced by AMD.
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