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The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.

In vivo degradation of RNA polymerase II largest subunit triggered by alpha-amanitin

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Nguyen, V.·1996·Nucleic Acids Research

Abstract

Alpha-Amanitin is a well-known specific inhibitor of RNA polymerase II (RNAPII) in vitro and in vivo. It is a cyclic octapeptide which binds with high affinity to the largest subunit of RNAPII, RPB1. We have found that in murine fibroblasts exposure to alpha-amanitin triggered degradation of the RPB1 subunit, while other RNAPII subunits, RPB5 and RPB8, remained almost unaffected. Transcriptional inhibition in alpha-amanitin-treated cells was slow and closely followed the disappearance of RPB1. The degradation rate of RPB1 was alpha-amanitin dose dependent and was not a consequence of transcriptional arrest. Alpha-Amanitin-promoted degradation of RPB1 was prevented in cells exposed to actinomycin D, another transcriptional inhibitor. Epitope-tagged recombinant human RPB1 subunits were expressed in mouse fibroblasts. In cells exposed to alpha-amanitin the wild-type recombinant subunit was degraded like the endogenous protein, but a mutated alpha-amanitin-resistant subunit remained unaffected. Hence, alpha-amanitin did not activate a proteolytic system, but instead its binding to mRPB1 likely represented a signal for degradation. Thus, in contrast to other inhibitors, such as actinomycin D or 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole, which reversibly act on transcription, inhibition by alpha-amanitin cannot be but an irreversible process because of the destruction of RNAPII.

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Metadata

Authors
Nguyen, V.
Venue
Nucleic Acids Research
Published
1996-08-01
Volume
24
Issue
15
Pages
2924-2929
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
OpenAlex
W1990213691
Cited by
265
References
51
FWCI
1.98
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: In vivo degradation of RNA polymerase II largest subunit triggered by alpha-amanitin. https://app.cochat.ai/papers/10.1093/nar/24.15.2924
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Nguyen, V. (1996). In vivo degradation of RNA polymerase II largest subunit triggered by alpha-amanitin. Nucleic Acids Research. https://doi.org/10.1093/nar/24.15.2924

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