Long RNA-Mediated Chromatin Regulation in Fission Yeast and Mammals

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.

Thirty Years with ERH: An mRNA Splicing and Mitosis Factor Only or Rather a Novel Genome Integrity Protector?

“…Erh1 and CCR4-NOT were also required for the assembly of the heterochromatin at the rDNA repeats to ensure its integrity [46]. Thus, in the vegetative cells, one way or the other, Erh1 seems to be involved in the formation of the several types of the facultative heterochromatin, which in the fission yeast is preferentially enriched for histone H3 with dimethylated lysine-9 [130]. In particular, Erh1 prevents the untimely expression of the meiotic genes by promoting both the assembly of the heterochromatin at their loci and the decay and nuclear retention of the transcripts in the non-meiotic cells.…”

“…The family member YTHDC1 (YT521-B) also forms multiple nuclear foci (YT bodies) and possesses the region encompassing the YTH domain with 24% identity to the region with YTH in Mmi1 [122,137]. This domain is used by Mmi1 to bind the unmethylated hexameric UU/C/GAAAC motif present in the meiotic mRNAs and also in several lncRNAs, and is dispensable for its interaction with Erh1 but, in the mouse embryonic stem cells, YTH of YTHDC1 recognizes the chromatin-associated retrotransposon transcripts hallmarked with the monomethylated adenosine (m 6 A) and is involved in the formation of the heterochromatin at their loci [37,122,125,130,138]. Interestingly, this process requires the N-methyltransferase SETDB1 that was reported to interact with the human ERH, albeit it generates the trimethylated lysine-9 on histone H3 instead of the dimethylated one that was associated with the Erh1 activity in S. pombe [46,116,130].…”

“…Thus, it seems that in humans the ERH function from S. pombe is extended to other lineage-specific genes, while the repression of the repetitive elements is the new one. Moreover, it is possible that ERH could also be involved in the formation of the heterochromatin mediated by chromatin-associated RNAs at transposon loci and during the inactivation of the whole chromosome X [130]. Regardless of the latter, ERH is required for transcriptional silencing in organisms ranging from the fission yeasts to humans.…”

ASAR lncRNAs control DNA replication timing through interactions with multiple hnRNP/RNA binding proteins

“…Chromosome-associated long non-protein coding RNAs are known to be important for numerous aspects of chromosome dynamics in diverse eukaryotes from yeast to mammals (Creamer et al, 2021; Ding et al, 2019; Faber and Vo, 2022; Menon and Meller, 2015; Nozawa and Gilbert, 2019). The mammalian nucleus is rich in heterogenous nuclear RNA (hnRNA), representing >95% of the total RNA Polymerase II output (Nozawa and Gilbert, 2019; St Laurent et al, 2012).…”

“…Chromosome-associated long non-coding RNAs are known to be important for numerous aspects of chromosome dynamics in diverse eukaryotes from yeast to mammals [10][11][12][13][14] . The mammalian nucleus is rich in heterogenous nuclear RNA (hnRNA), which represents >95% of the total RNA Polymerase II output 12,15 .…”