Causes and consequences of RNA polymerase II stalling during transcript elongation

Area of Science:

• Molecular Biology
• Gene Expression
• Genome Stability

Background:

• Transcript elongation by RNA polymerase II (Pol II) is frequently interrupted by various intrinsic and extrinsic obstacles.
• These roadblocks include promoter-proximal pausing, nucleosomes, RNA structures, DNA sequence, transcribing polymerases, replication machinery, and DNA damage.

Purpose of the Study:

• To review the cellular mechanisms for distinguishing and resolving different RNA polymerase II stalling contexts.
• To explore the consequences of unresolved Pol II roadblocks on genome stability.

Main Methods:

• Review of existing literature on RNA polymerase II transcription, elongation, stalling, and repair pathways.
• Analysis of cellular responses to diverse transcriptional impediments.

Main Results:

• Cells possess sophisticated systems to differentiate between various Pol II stalling triggers.
• Resolution strategies range from simple backtracking and RNA cleavage (facilitated by TFIIS) to complex pathways involving transcription termination or protein degradation.
• Unresolved stalls can lead to significant genome instability.

Conclusions:

• The cell actively manages Pol II stalling through diverse, context-specific resolution mechanisms.
• Effective resolution of transcriptional roadblocks is crucial for maintaining genome integrity.