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Abstract:
Pervasive transcription of eukaryotic genomes
stems to a large extent from bidirectional promoters
that synthesize mRNA and divergent noncoding RNA
(ncRNA). Here, we show that ncRNA transcription in
the yeast S. cerevisiae is globally restricted by early
termination that relies on the essential RNA-binding
factor Nrd1. Depletion of Nrd1 from the nucleus
results in 1,526 Nrd1-unterminated transcripts
(NUTs) that originate from nucleosome-depleted regions
(NDRs) and can deregulate mRNA synthesis
by antisense repression and transcription interference.
Transcriptome-wide Nrd1-binding maps reveal
divergent NUTs at most promoters and antisense
NUTs in most 30 regions of genes. Nrd1 and its partner
Nab3 preferentially bind RNA motifs that are
depleted in mRNAs and enriched in ncRNAs and
some mRNAs whose synthesis is controlled by
transcription attenuation. These results define a
global mechanism for transcriptome surveillance
that selectively terminates ncRNA synthesis to provide
promoter directionality and to suppress antisense
transcription.
