ATP-dependent Chromatin Remodeling Shapes the Long Noncoding RNA Landscape

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2014 Nov 5

PMID 25367034

Citations 35

Authors

Eric A Alcid

Toshio Tsukiyama

Affiliations

Soon will be listed here.

Abstract

Long noncoding RNAs (lncRNAs) are pervasively transcribed across eukaryotic genomes, but functions of only a very small subset of them have been demonstrated. This has led to active debate about whether many of them have any biological functions. In addition, very few regulators of lncRNAs have been identified. We developed a novel genetic screen using reconstituted RNAi in Saccharomyces cerevisiae and systematically identified a large number of putative lncRNA repressors. Among them, we found that four highly conserved chromatin remodeling factors are global lncRNA repressors that play major roles in shaping the eukaryotic lncRNA transcriptome. Importantly, we identified >250 antisense lncRNAs (CRRATs [chromatin remodeling-repressed antisense transcripts]) whose repression by these chromatin remodeling factors is required for the maintenance of normal levels of overlapping mRNA transcripts. Our results strongly suggest that regulation of mRNA through repression of antisense lncRNAs is far more broadly used than previously appreciated.

Citing Articles

Convergence of coronary artery disease genes onto endothelial cell programs.

Schnitzler G, Kang H, Fang S, Angom R, Lee-Kim V, Ma X Nature. 2024; 626(8000):799-807.

PMID: 38326615 PMC: 10921916. DOI: 10.1038/s41586-024-07022-x.

RSC and GRFs confer promoter directionality by restricting divergent noncoding transcription.

Wu A, Vivori C, Patel H, Sideri T, Moretto F, van Werven F Life Sci Alliance. 2022; 5(12).

PMID: 36114005 PMC: 9481977. DOI: 10.26508/lsa.202201394.

Roles of long noncoding RNAs and small extracellular vesicle-long noncoding RNAs in type 2 diabetes.

Chang W, Wang M, Zhang Y, Yu F, Hu B, Goljanek-Whysall K Traffic. 2022; 23(11):526-537.

PMID: 36109347 PMC: 9828071. DOI: 10.1111/tra.12868.

A hexasome is the preferred substrate for the INO80 chromatin remodeling complex, allowing versatility of function.

Hsieh L, Gourdet M, Moore C, Munoz E, Gamarra N, Ramani V Mol Cell. 2022; 82(11):2098-2112.e4.

PMID: 35597239 PMC: 9351570. DOI: 10.1016/j.molcel.2022.04.026.

The Hda1 histone deacetylase limits divergent non-coding transcription and restricts transcription initiation frequency.

Gowthaman U, Ivanov M, Schwarz I, Patel H, Muller N, Garcia-Pichardo D EMBO J. 2021; 40(23):e108903.

PMID: 34661296 PMC: 8634119. DOI: 10.15252/embj.2021108903.

References

Anders S, Pyl P, Huber W . HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2014; 31(2):166-9. PMC: 4287950. DOI: 10.1093/bioinformatics/btu638. View

Carrozza M, Li B, Florens L, Suganuma T, Swanson S, Lee K . Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell. 2005; 123(4):581-92. DOI: 10.1016/j.cell.2005.10.023. View

Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z . GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics. 2009; 10:48. PMC: 2644678. DOI: 10.1186/1471-2105-10-48. View

Albert I, Mavrich T, Tomsho L, Qi J, Zanton S, Schuster S . Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome. Nature. 2007; 446(7135):572-6. DOI: 10.1038/nature05632. View

Van de Vosse D, Wan Y, Lapetina D, Chen W, Chiang J, Aitchison J . A role for the nucleoporin Nup170p in chromatin structure and gene silencing. Cell. 2013; 152(5):969-83. PMC: 3690833. DOI: 10.1016/j.cell.2013.01.049. View

Yadon A, Van de Mark D, Basom R, Delrow J, Whitehouse I, Tsukiyama T . Chromatin remodeling around nucleosome-free regions leads to repression of noncoding RNA transcription. Mol Cell Biol. 2010; 30(21):5110-22. PMC: 2953044. DOI: 10.1128/MCB.00602-10. View

Zofall M, Fischer T, Zhang K, Zhou M, Cui B, Veenstra T . Histone H2A.Z cooperates with RNAi and heterochromatin factors to suppress antisense RNAs. Nature. 2009; 461(7262):419-22. PMC: 2746258. DOI: 10.1038/nature08321. View

Tsai M, Manor O, Wan Y, Mosammaparast N, Wang J, Lan F . Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010; 329(5992):689-93. PMC: 2967777. DOI: 10.1126/science.1192002. View

Goldstein A, McCusker J . Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae. Yeast. 1999; 15(14):1541-53. DOI: 10.1002/(SICI)1097-0061(199910)15:14<1541::AID-YEA476>3.0.CO;2-K. View

10.

Camblong J, Beyrouthy N, Guffanti E, Schlaepfer G, Steinmetz L, Stutz F . Trans-acting antisense RNAs mediate transcriptional gene cosuppression in S. cerevisiae. Genes Dev. 2009; 23(13):1534-45. PMC: 2704465. DOI: 10.1101/gad.522509. View

11.

Venters B, Pugh B . Genomic organization of human transcription initiation complexes. Nature. 2013; 502(7469):53-8. PMC: 4018585. DOI: 10.1038/nature12535. View

12.

Drinnenberg I, Fink G, Bartel D . Compatibility with killer explains the rise of RNAi-deficient fungi. Science. 2011; 333(6049):1592. PMC: 3790311. DOI: 10.1126/science.1209575. View

13.

Kobor M, Venkatasubrahmanyam S, Meneghini M, Gin J, Jennings J, Link A . A protein complex containing the conserved Swi2/Snf2-related ATPase Swr1p deposits histone variant H2A.Z into euchromatin. PLoS Biol. 2004; 2(5):E131. PMC: 374244. DOI: 10.1371/journal.pbio.0020131. View

14.

Xu Z, Wei W, Gagneur J, Perocchi F, Clauder-Munster S, Camblong J . Bidirectional promoters generate pervasive transcription in yeast. Nature. 2009; 457(7232):1033-7. PMC: 2766638. DOI: 10.1038/nature07728. View

15.

Papamichos-Chronakis M, Watanabe S, Rando O, Peterson C . Global regulation of H2A.Z localization by the INO80 chromatin-remodeling enzyme is essential for genome integrity. Cell. 2011; 144(2):200-13. PMC: 3035940. DOI: 10.1016/j.cell.2010.12.021. View

16.

Sultan M, Dokel S, Amstislavskiy V, Wuttig D, Sultmann H, Lehrach H . A simple strand-specific RNA-Seq library preparation protocol combining the Illumina TruSeq RNA and the dUTP methods. Biochem Biophys Res Commun. 2012; 422(4):643-6. DOI: 10.1016/j.bbrc.2012.05.043. View

17.

Djebali S, Davis C, Merkel A, Dobin A, Lassmann T, Mortazavi A . Landscape of transcription in human cells. Nature. 2012; 489(7414):101-8. PMC: 3684276. DOI: 10.1038/nature11233. View

18.

Neil H, Malabat C, dAubenton-Carafa Y, Xu Z, Steinmetz L, Jacquier A . Widespread bidirectional promoters are the major source of cryptic transcripts in yeast. Nature. 2009; 457(7232):1038-42. DOI: 10.1038/nature07747. View

19.

Core L, Waterfall J, Lis J . Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science. 2008; 322(5909):1845-8. PMC: 2833333. DOI: 10.1126/science.1162228. View

20.

Tong A, Evangelista M, Parsons A, Xu H, Bader G, Page N . Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science. 2001; 294(5550):2364-8. DOI: 10.1126/science.1065810. View