Causes and consequences of RNA polymerase II stalling during transcript elongation
- 1 January 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Molecular Cell Biology
- Vol. 22 (1), 3-21
- https://doi.org/10.1038/s41580-020-00308-8
Abstract
The journey of RNA polymerase II (Pol II) as it transcribes a gene is anything but a smooth ride. Transcript elongation is discontinuous and can be perturbed by intrinsic regulatory barriers, such as promoter-proximal pausing, nucleosomes, RNA secondary structures and the underlying DNA sequence. More substantial blocking of Pol II translocation can be caused by other physiological circumstances and extrinsic obstacles, including other transcribing polymerases, the replication machinery and several types of DNA damage, such as bulky lesions and DNA double-strand breaks. Although numerous different obstacles cause Pol II stalling or arrest, the cell somehow distinguishes between them and invokes different mechanisms to resolve each roadblock. Resolution of Pol II blocking can be as straightforward as temporary backtracking and transcription elongation factor S-II (TFIIS)-dependent RNA cleavage, or as drastic as premature transcription termination or degradation of polyubiquitylated Pol II and its associated nascent RNA. In this Review, we discuss the current knowledge of how these different Pol II stalling contexts are distinguished by the cell, how they overlap with each other, how they are resolved and how, when unresolved, they can cause genome instability. Transcript elongation by RNA polymerase II can be perturbed by barriers such as promoter-proximal pausing and nucleosomes and by obstacles such as the replication machinery and DNA lesions. Recent studies revealed how different contexts of RNA polymerase II stalling are distinguished and resolved, and how unresolved stalling can cause genome instability.This publication has 211 references indexed in Scilit:
- Ubiquitylation and degradation of elongating RNA polymerase II: The last resortBiochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 2013
- Senataxin Associates with Replication Forks to Protect Fork Integrity across RNA-Polymerase-II-Transcribed GenesCell, 2012
- Cdc48/p97 Mediates UV-Dependent Turnover of RNA Pol IIMolecular Cell, 2011
- Yeast Sen1 Helicase Protects the Genome from Transcription-Associated InstabilityMolecular Cell, 2011
- ATM-Dependent Chromatin Changes Silence Transcription In cis to DNA Double-Strand BreaksCell, 2010
- The Human PAF1 Complex Acts in Chromatin Transcription Elongation Both Independently and Cooperatively with SII/TFIISCell, 2010
- Dynamic Regulation of Nucleosome Positioning in the Human GenomeCell, 2008
- Nature of the Nucleosomal Barrier to RNA Polymerase IIMolecular Cell, 2005
- A Ratchet Mechanism of Transcription Elongation and Its ControlCell, 2005
- Cotranscriptionally Formed DNA:RNA Hybrids Mediate Transcription Elongation Impairment and Transcription-Associated RecombinationMolecular Cell, 2003