Abstract
Long noncoding RNAs (lncRNAs), which are longer than 200 nucleotides but often unstable, contribute a substantial and diverse portion to pervasive noncoding transcriptomes. Most lncRNAs are poorly annotated and understood, although several play important roles in gene regulation and diseases. Here we systematically uncover and analyze lncRNAs in Schizosaccharomyces pombe. Based on RNA-seq data from twelve RNA-processing mutants and nine physiological conditions, we identify 5775 novel lncRNAs, nearly 4× the previously annotated lncRNAs. The expression of most lncRNAs becomes strongly induced under the genetic and physiological perturbations, most notably during late meiosis. Most lncRNAs are cryptic and suppressed by three RNA-processing pathways: the nuclear exosome, cytoplasmic exonuclease, and RNAi. Double-mutant analyses reveal substantial coordination and redundancy among these pathways. We classify lncRNAs by their dominant pathway into cryptic unstable transcripts (CUTs), Xrn1-sensitive unstable transcripts (XUTs), and Dicer-sensitive unstable transcripts (DUTs). XUTs and DUTs are enriched for antisense lncRNAs, while CUTs are often bidirectional and actively translated. The cytoplasmic exonuclease, along with RNAi, dampens the expression of thousands of lncRNAs and mRNAs that become induced during meiosis. Antisense lncRNA expression mostly negatively correlates with sense mRNA expression in the physiological, but not the genetic conditions. Intergenic and bidirectional lncRNAs emerge from nucleosome-depleted regions, upstream of positioned nucleosomes. Our results highlight both similarities and differences to lncRNA regulation in budding yeast. This broad survey of the lncRNA repertoire and characteristics in S. pombe, and the interwoven regulatory pathways that target lncRNAs, provides a rich framework for their further functional analyses.
Highlights
Genomes are more pervasively transcribed than expected from their protein-coding sequences
Consistent with the cytoplasmic exonuclease acting as a backup system, we find that many cryptic unstable transcripts (CUTs) and Dicer-sensitive unstable transcripts (DUTs) are targeted by Exo2 and the NMD factor Upf1 (Figs. 2, 4C)
This study increases the number of Long noncoding RNAs (lncRNAs) annotated in fission yeast by almost fivefold, revealing both similarities and striking differences to lncRNA characteristics and regulation budding yeast
Summary
Genomes are more pervasively transcribed than expected from their protein-coding sequences. Over 80% of the human genome is transcribed but only ∼2% encodes proteins (Hangauer et al 2013). -called long noncoding RNAs (lncRNAs), which exceed 200 nucleotides (nt) in length but lack long open reading frames, make up a sub-. The act of transcription rather than the lncRNA itself is functionally relevant (Ard et al 2017). The lncRNAs are often lowly expressed but show more changes in expression levels between different tissues or conditions than do the protein-coding messenger RNAs (mRNAs)
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