Long noncoding RNA repertoire and targeting by nuclear exosome, cytoplasmic exonuclease, and RNAi in fission yeast.

Long noncoding RNA repertoire and targeting by nuclear exosome, cytoplasmic exonuclease, and RNAi in fission yeast.
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DOI:
10.1261/rna.065524.118
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发表时间:
2018-09
期刊:
RNA (New York, N.Y.)
影响因子:
--
通讯作者:
Bähler J
Bähler J
中科院分区:
其他
文献类型:
--
作者:
Atkinson SR;Marguerat S;Bitton DA;Rodríguez-López M;Rallis C;Lemay JF;Cotobal C;Malecki M;Smialowski P;Mata J;Korber P;Bachand F;Bähler J

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长链非编码RNA(lncRNA),长度超过200个核苷酸,但往往不稳定,贡献了大量的和不同的部分普遍的非编码转录组。大多数lncRNA的注释和理解很少,尽管有几个在基因调控和疾病中发挥重要作用。在这里,我们系统地发现和分析lncRNA在裂殖酵母粟酒裂殖酵母。基于12个RNA加工突变体和9种生理条件下的RNA-seq数据,我们鉴定了5775个新的lncRNA,几乎是以前注释的lncRNA的4倍。大多数lncRNA的表达在遗传和生理扰动下被强烈诱导,最显著的是在减数分裂后期。大多数lncRNA是隐蔽的,并被三种RNA加工途径抑制:核外泌体、细胞质外切核酸酶和RNAi。双突变体分析揭示了这些途径之间的大量协调和冗余。我们将lncRNA按其主导途径分为隐蔽不稳定转录本(CUT)、Xrn 1敏感不稳定转录本(XUT)和Dicer敏感不稳定转录本(DUT)。XUT和DUT富含反义lncRNA,而CUT通常是双向的并且被主动翻译。细胞质核酸外切酶沿着RNAi抑制减数分裂期间诱导的数千种lncRNA和mRNA的表达。在生理条件下,反义lncRNA的表达与正义mRNA的表达大多呈负相关,但与遗传条件无关。基因间和双向lncRNA出现从核小体耗尽区域,定位核小体的上游。我们的研究结果突出了芽殖酵母中lncRNA调控的相似性和差异。本文对S.粟酒裂殖酵母和靶向lncRNA的相互交织的调节途径为其进一步的功能分析提供了丰富的框架。
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.
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