scholarly journals Long RNA-Mediated Chromatin Regulation in Fission Yeast and Mammals

2022 ◽  
Vol 23 (2) ◽  
pp. 968
Author(s):  
Matthew W. Faber ◽  
Tommy V. Vo

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.

2011 ◽  
Vol 22 (1) ◽  
pp. 66-77 ◽  
Author(s):  
Nicole Cremona ◽  
Kristine Potter ◽  
Jo Ann Wise

To determine the relative importance of transcriptional regulation versus RNA processing and turnover during the transition from proliferation to meiotic differentiation in the fission yeast Schizosaccharomyces pombe, we analyzed temporal profiles and effects of RNA surveillance factor mutants on expression of 32 meiotic genes. A comparison of nascent transcription with steady-state RNA accumulation reveals that the vast majority of these genes show a lag between maximal RNA synthesis and peak RNA accumulation. During meiosis, total RNA levels parallel 3′ processing, which occurs in multiple, temporally distinct waves that peak from 3 to 6 h after meiotic induction. Most early genes and one middle gene, mei4, share a regulatory mechanism in which a specialized RNA surveillance factor targets newly synthesized transcripts for destruction. Mei4p, a member of the forkhead transcription factor family, in turn regulates a host of downstream genes. Remarkably, a spike in transcription is observed for less than one-third of the genes surveyed, and even these show evidence of RNA-level regulation. In aggregate, our findings lead us to propose that a regulatory cascade driven by changes in processing and stability of newly synthesized transcripts operates alongside the well-known transcriptional cascade as fission yeast cells enter meiosis.


2015 ◽  
Vol 108 (2) ◽  
pp. 538a
Author(s):  
Takeshi Sugawara ◽  
Kenta Masuda ◽  
Jun-ichi Uewaki ◽  
Akinori Awazu ◽  
Hiraku Nishimori ◽  
...  

Open Biology ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 170261 ◽  
Author(s):  
Kenichi Sajiki ◽  
Yuria Tahara ◽  
Alejandro Villar-Briones ◽  
Tomáš Pluskal ◽  
Takayuki Teruya ◽  
...  

Rapamycin inhibits TOR (target of rapamycin) kinase, and is being used clinically to treat various diseases ranging from cancers to fibrodysplasia ossificans progressiva. To understand rapamycin mechanisms of action more comprehensively, 1014 temperature-sensitive (ts) fission yeast ( Schizosaccharomyces pombe ) mutants were screened in order to isolate strains in which the ts phenotype was rescued by rapamycin. Rapamycin-rescued 45 strains, among which 12 genes responsible for temperature sensitivity were identified. These genes are involved in stress-activated protein kinase (SAPK) signalling, chromatin regulation, vesicle transport, and CoA- and mevalonate-related lipid metabolism. Subsequent metabolome analyses revealed that rapamycin upregulated stress-responsive metabolites, while it downregulated purine biosynthesis intermediates and nucleotide derivatives. Rapamycin alleviated abnormalities in cell growth and cell division caused by sty1 mutants (Δ sty1 ) of SAPK. Notably, in Δ sty1 , rapamycin reduced greater than 75% of overproduced metabolites (greater than 2× WT), like purine biosynthesis intermediates and nucleotide derivatives, to WT levels. This suggests that these compounds may be the points at which the SAPK/TOR balance regulates continuous cell proliferation. Rapamycin might be therapeutically useful for specific defects of these gene functions.


2017 ◽  
Vol 23 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Daniel A. Lorenz ◽  
Steve Vander Roest ◽  
Martha J. Larsen ◽  
Amanda L. Garner

microRNAs (miRNAs) are small gene regulatory RNAs, and their expression has been found to be dysregulated in a number of human diseases. To facilitate the discovery of small molecules capable of selectively modulating the activity of a specific miRNA, we have utilized new high-throughput screening technology targeting Dicer-mediated pre-miRNA maturation. Pilot screening of ~50,000 small molecules and ~33,000 natural product extract libraries against pre-miR-21 processing indicated the potential of our assay for this goal, yielding a campaign Z′ factor of 0.52 and an average plate signal-to-background (S/B) ratio of 13. Using two-dimensional screening against a second pre-miRNA, pre-let-7d, we evaluated the selectivity of confirmed hits. The results presented demonstrate how high-throughput screening can be used to identify selective small molecules for a target RNA.


Reproduction ◽  
2018 ◽  
Vol 156 (2) ◽  
pp. R9-R21 ◽  
Author(s):  
H M McSwiggin ◽  
A M O’Doherty

Infertility is an often devastating diagnosis encountered by around one in six couples who are trying to conceive. Moving away from the long-held belief that infertility is primarily a female issue, it is now recognised that half, if not more, of these cases may be due to male factors. Recent evidence has suggested that epigenetic abnormalities in chromatin dynamics, DNA methylation or sperm-borne RNAs may contribute to male infertility. In light of advances in deep sequencing technologies, researchers have been able to increase the coverage and depth of sequencing results, which in turn has allowed more comprehensive analyses of spermatozoa chromatin dynamics and methylomes and enabled the discovery of new subsets of sperm RNAs. This review examines the most current literature related to epigenetic processes in the male germline and the associations of aberrant modifications with fertility and development.


2007 ◽  
Vol 17 (3) ◽  
pp. 273-279 ◽  
Author(s):  
Thomas E Edwards ◽  
Daniel J Klein ◽  
Adrian R Ferré-D’Amaré

PLoS Genetics ◽  
2015 ◽  
Vol 11 (4) ◽  
pp. e1005136 ◽  
Author(s):  
Eric M. Camino ◽  
John C. Butts ◽  
Alison Ordway ◽  
Jordan E. Vellky ◽  
Mark Rebeiz ◽  
...  

EMBO Reports ◽  
2017 ◽  
Vol 18 (7) ◽  
pp. 1263-1263 ◽  
Author(s):  
Ayano Kagami ◽  
Takeshi Sakuno ◽  
Yuya Yamagishi ◽  
Tadashi Ishiguro ◽  
Tatsuya Tsukahara ◽  
...  

2018 ◽  
Author(s):  
Benjamin Kleaveland ◽  
Charlie Y. Shi ◽  
Joanna Stefano ◽  
David P. Bartel

SUMMARYNoncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs—a long ncRNA, a circular RNA, and two microRNAs—using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more efficient than previously described examples of target-directed microRNA degradation, which come from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7–targeted mRNAs and enables the accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network.HIGHLIGHTSA long noncoding RNA, a circular RNA, and two microRNAs form a regulatory networkThe Cyrano long noncoding RNA directs potent, multiple-turnover destruction of miR-7Unchecked miR-7 prevents accumulation of Cdr1as circular RNA in cytoplasm of neurons miR-7 prevents this accumulation by enhancing the miR-671-directed slicing of Cdr1as


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