Epigenetic regulation of TERRA transcription and metacyclogenesis by base J inLeishmania major

Abstract

ABSTRACTThe hyper-modified DNA base J helps control termination of Pol II transcription at polycistronic transcription units (PTUs) inT. bruceiandL. major, allowing epigenetic control of gene expression. The Telomere Repeat-containing RNA (TERRA) is synthesized inT. bruceiby Pol I readthrough transcription of a telomeric PTU. While little is understood regarding TERRA synthesis and function, the hyper-modified DNA base J is highly enriched at telomeres inL. majorpromastigotes. We now show that TERRA is synthesized by Pol II inL. majorand loss of base J leads to increased TERRA. For at least one site, the increased TERRA is by Pol II readthrough transcription from an adjacent PTU. Furthermore, Pol II readthrough defects and increased TERRA correlate with increased differentiation of promastigotes to the infectious metacyclic life stage and decreased cell viability. These results help explain the essential nature of base J inLeishmaniaand provide insight regarding epigenetic control of coding and non-coding RNA expression and parasite development during the life cycle ofL. major.