Terminator-dependent facilitated recycling of RNA polymerase III provides gene-specific transcriptional activation in vivo.

Abstract

Genes transcribed by the RNA polymerase (Pol) III of yeast are mostly found at sites of high transcription, genomic fragility, and replication fork stalling. Transcription terminator-dependent facilitated recycling of Pol III on naked DNA templates boosts transcription in vitro; its operability in vivo is not known. Recycling on the same template links transcriptional output directly to the reinitiation frequency. Using recycling-deficient Pol III or terminator-deficient templates, we found that terminator is essential to couple the facilitated Pol III recycling and chromatin remodeling for achieving high transcriptional activation. Mechanism of the full activation process constitutes three linked steps, antirepression, chromatin remodeling, and Pol III recycling. Normally high transcriptional demands are met by the terminator-facilitated Pol III recycling on genes, while different recycling frequencies result in different Pol III occupancies and gene-specific transcript yields. Abnormal increase in recycling frequency may cause the genomic sites fragility in normal cells or highly elevated Pol III transcription in cancerous cells or other related disorders.