Xrn2 substrate mapping identifies torpedo loading sites and extensive premature termination of RNA pol II transcription.

ABSTRACT: The exonuclease torpedo Xrn2 loads onto nascent RNA 5'-PO₄ ends and chases down pol II to promote termination downstream from polyA sites. We report that Xrn2 is recruited to preinitiation complexes and "travels" to 3' ends of genes. Mapping of 5'-PO₄ ends in nascent RNA identified Xrn2 loading sites stabilized by an active site mutant, Xrn2(D235A). Xrn2 loading sites are approximately two to 20 bases downstream from where CPSF73 cleaves at polyA sites and histone 3' ends. We propose that processing of all mRNA 3' ends comprises cleavage and limited 5'-3' trimming by CPSF73, followed by handoff to Xrn2. A similar handoff occurs at tRNA 3' ends, where cotranscriptional RNase Z cleavage generates novel Xrn2 substrates. Exonuclease-dead Xrn2 increased transcription in 3'

SUBMITTER: Cortazar MA 

PROVIDER: S-EPMC9744234 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature