Effects of Hydrogen Peroxide Stress on the Nucleolar Redox Environment and Pre-rRNA Maturation
Identifying biologically relevant molecular targets of oxidative stress may provide new insights into disease mechanisms and accelerate development of novel biomarkers. Ribosome biogenesis is a fundamental prerequisite for cellular protein synthesis, but how oxidative stress affects ribosome biogene...
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| Published in: | Frontiers in molecular biosciences Vol. 8; p. 678488 |
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| Main Authors: | , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Switzerland
Frontiers Media S.A
26-04-2021
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Identifying biologically relevant molecular targets of oxidative stress may provide new insights into disease mechanisms and accelerate development of novel biomarkers. Ribosome biogenesis is a fundamental prerequisite for cellular protein synthesis, but how oxidative stress affects ribosome biogenesis has not been clearly established. To monitor and control the redox environment of ribosome biogenesis, we targeted a redox-sensitive roGFP reporter and catalase, a highly efficient H
O
scavenger, to the nucleolus, the primary site for transcription and processing of rRNA in eukaryotic cells. Imaging of mouse 3T3 cells exposed to non-cytotoxic H
O
concentrations revealed increased oxidation of the nucleolar environment accompanied by a detectable increase in the oxidative damage marker 8-oxo-G in nucleolar RNA. Analysis of pre-rRNA processing showed a complex pattern of alterations in pre-rRNA maturation in the presence of H
O
, including inhibition of the transcription and processing of the primary 47S transcript, accumulation of 18S precursors, and inefficient 3'-end processing of 5.8S rRNA. This work introduces new tools for studies of the redox biology of the mammalian nucleolus and identifies pre-rRNA maturation steps sensitive to H
O
stress. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Jessica Willi, Northwestern University, United States; Vikram Govind Panse, ETH Zürich, Switzerland Edited by: Norbert Polacek, University of Bern, Switzerland This article was submitted to Protein and RNA Networks, a section of the journal Frontiers in Molecular Biosciences |
| ISSN: | 2296-889X 2296-889X |
| DOI: | 10.3389/fmolb.2021.678488 |