Transcriptome surveillance by selective termination of noncoding RNA synthesis.

Area of Science:

• Genetics
• Molecular Biology
• RNA Biology

Background:

• Eukaryotic genomes exhibit pervasive transcription from bidirectional promoters, producing both mRNA and noncoding RNA (ncRNA).
• The precise regulation of ncRNA synthesis and its impact on mRNA production remain key areas of investigation.

Purpose of the Study:

• To investigate the global mechanism restricting ncRNA transcription in yeast Saccharomyces cerevisiae.
• To identify the role of the RNA-binding factor Nrd1 in this regulatory process.

Main Methods:

• Depletion of the essential RNA-binding factor Nrd1 from yeast nuclei.
• Transcriptome-wide mapping of Nrd1 binding sites.
• Analysis of Nrd1-unterminated transcripts (NUTs) and their genomic locations.

Main Results:

• Depletion of Nrd1 led to the accumulation of 1,526 Nrd1-unterminated transcripts (NUTs), primarily originating from nucleosome-depleted regions (NDRs).
• These NUTs were found at divergent promoters and in the 3' regions of genes, suggesting a global role in transcriptome regulation.
• Nrd1 and Nab3 bind specific RNA motifs enriched in ncRNAs and some mRNAs, indicating a mechanism for selective termination.

Conclusions:

• Nrd1-mediated early termination is a global mechanism that restricts ncRNA synthesis in yeast.
• This process ensures promoter directionality and suppresses antisense transcription, thereby preventing deregulation of mRNA synthesis.
• The findings reveal a critical pathway for transcriptome surveillance and RNA homeostasis.