Transcription termination and nuclear degradation of cryptic unstable transcripts: A role for the Nrd1-Nab3 pathway in genome surveillance

Cryptic unstable transcripts (CUTs) are widely distributed in the genome of S. cerevisiae. These RNAs generally derive from nonannotated regions of the genome and are degraded rapidly and efficiently by the nuclear exosome via a pathway that involves degradative polyadenylation by a new poly(A) polymerase borne by the TRAMP complex. What is the share of significant information that is encrypted in CUTs and what distinguishes a CUT from other Pol II transcripts are unclear to date. Here we report the dissection of the molecular mechanism that leads to degradation of a model CUT, NEL025c. We show that the Nrd1p-Nab3p-dependent pathway, involved in transcription termination of sno/ snRNAs, is required, albeit not sufficient, for efficient degradation of NEL025c RNAs and at least a subset of other CUTs. Our results suggest an important role for the Nrd1p-Nab3p pathway in the control of gene expression throughout the genome.