Abstract
As part of a complex network of genome control, long regulatory RNAs exert significant influences on chromatin dynamics. Understanding how this occurs could illuminate new avenues for disease treatment and lead to new hypotheses that would advance gene regulatory research. Recent studies using the model fission yeast Schizosaccharomyces pombe (S. pombe) and powerful parallel sequencing technologies have provided many insights in this area. This review will give an overview of key findings in S. pombe that relate long RNAs to multiple levels of chromatin regulation: histone modifications, gene neighborhood regulation in cis and higher-order chromosomal ordering. Moreover, we discuss parallels recently found in mammals to help bridge the knowledge gap between the study systems.
Highlights
From yeast to mammals, eukaryotic genomes can be pervasively transcribed depending on developmental or environmental states
Small noncoding RNAs are less than 200 nucleotides in length and are comprised of major subclasses, including microRNAs, short interfering RNAs, tRNA-derived small RNAs and piwi-interacting RNAs
The exact modes of RNA recognition and binding are different between the homologs S. pombe Mmi1 and mammalian YT521-B homology (YTH) Domain Containing 1 (YTHDC1), which bind to Determinant of Selective Removal (DSR) motifs and m6A, respectively [54,55], these conserved proteins can use long RNAs to mediate similar repressive functions
Summary
Eukaryotic genomes can be pervasively transcribed depending on developmental or environmental states. Small noncoding RNAs are less than 200 nucleotides in length and are comprised of major subclasses, including microRNAs (miRNAs), short interfering RNAs (siRNAs), tRNA-derived small RNAs (tsRNAs) and piwi-interacting RNAs (piRNAs) Their roles in transcriptome and chromatin regulation have been extensively reviewed elsewhere and will not be the focus of this review [3,4,5,6,7,8]. This review will focus on chromatin regulatory roles of long RNAs, irrespective of whether they might be bona fide lncRNAs or bifRNAs. In recent years, the combination of facile genetics, molecular biology and biochemistry with high-throughput sequencing approaches has enabled the fission yeast S. pombe to become an outstanding model for understanding the regulatory functions of nuclear long RNAs. Excitingly, studies in mammalian mouse and human models are beginning to reveal similar mechanisms of long RNA action at the chromatin level. This review will summarize our latest knowledge on how fission yeast and mammals leverage long RNAs to elicit conserved mechanisms of genome control
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