Targeting Xist with compounds that disrupt RNA structure and X inactivation.


Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
04 2022
Historique:
received: 27 11 2019
accepted: 08 02 2022
pubmed: 1 4 2022
medline: 19 4 2022
entrez: 31 3 2022
Statut: ppublish

Résumé

Although more than 98% of the human genome is non-coding

Identifiants

pubmed: 35355011
doi: 10.1038/s41586-022-04537-z
pii: 10.1038/s41586-022-04537-z
doi:

Substances chimiques

Histones 0
RNA, Long Noncoding 0
XIST non-coding RNA 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

160-166

Subventions

Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Références

Consortium, E. P. et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799–816 (2007).
doi: 10.1038/nature05874
Santos, R. et al. A comprehensive map of molecular drug targets. Nat. Rev. Drug Discov. 16, 19–34 (2017).
doi: 10.1038/nrd.2016.230
Warner, K. D. et al. Principles for targeting RNA with drug-like small molecules. Nat. Rev. Drug Discov. 17, 547–558 (2018).
doi: 10.1038/nrd.2018.93
Zhang, F. & Lupski, J. R. Non-coding genetic variants in human disease. Hum. Mol. Genet. 24, R102–R110 (2015).
doi: 10.1093/hmg/ddv259
Lee, J. T. Epigenetic regulation by long noncoding RNAs. Science 338, 1435–1439 (2012).
doi: 10.1126/science.1231776
Wutz, A. et al. Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nat. Genet. 30, 167–174 (2002).
doi: 10.1038/ng820
Rizvi, N. F. & Smith, G. F. RNA as a small molecule druggable target. Bioorg. Med. Chem. Lett. 27, 5083–5088 (2017).
doi: 10.1016/j.bmcl.2017.10.052
Disney, M. D. et al. Drugging the RNA world. Cold Spring Harb. Perspect. Biol. 10, a034769 (2018).
doi: 10.1101/cshperspect.a034769
Howe, J. A. et al. Selective small-molecule inhibition of an RNA structural element. Nature 526, 672–677 (2015).
doi: 10.1038/nature15542
Palacino, J. et al. SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice. Nat. Chem. Biol. 11, 511–517 (2015).
doi: 10.1038/nchembio.1837
Disney, M. D. et al. Inforna 2.0: a platform for the sequence-based design of small molecules targeting structured RNAs. ACS Chem. Biol. 11, 1720–1728 (2016).
doi: 10.1021/acschembio.6b00001
Allen Annis, D. et al. An affinity selection-mass spectrometry method for the identification of small molecule ligands from self-encoded combinatorial libraries—Discovery of a novel antagonist of E-coli dihydrofolate reductase. Int. J. Mass Spectrom. 238, 77–83 (2004).
Rizvi, N. F. et al. Discovery of selective RNA-binding small molecules by affinity-selection mass spectrometry. ACS Chem. Biol. 13, 820–831 (2018).
doi: 10.1021/acschembio.7b01013
Rizvi, N. F. et al. Targeting RNA with small molecules: identification of selective, RNA-binding small molecules occupying drug-like chemical space. SLAS Discov. 25, 384–396 (2020).
Cifuentes-Rojas, C. et al. Regulatory interactions between RNA and polycomb repressive complex 2. Mol. Cell 55, 171–185 (2014).
doi: 10.1016/j.molcel.2014.05.009
Chillon, I. et al. Native purification and analysis of long RNAs. Methods Enzymol. 558, 3–37 (2015).
doi: 10.1016/bs.mie.2015.01.008
Lipinski, C. A. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov. Today Technol. 1, 337–341 (2004).
doi: 10.1016/j.ddtec.2004.11.007
Monfort, A. et al. Identification of Spen as a crucial factor for Xist function through forward genetic screening in haploid embryonic stem cells. Cell Rep. 12, 554–561 (2015).
doi: 10.1016/j.celrep.2015.06.067
Lee, M. K. et al. A novel small-molecule binds to the influenza A virus RNA promoter and inhibits viral replication. Chem. Commun. 50, 368–370 (2014).
doi: 10.1039/C3CC46973E
Ogawa, Y. et al. Intersection of the RNA interference and X-inactivation pathways. Science 320, 1336–1341 (2008).
doi: 10.1126/science.1157676
Zhao, J. et al. Genome-wide identification of polycomb-associated RNAs by RIP–seq. Mol. Cell 40, 939–953 (2010).
doi: 10.1016/j.molcel.2010.12.011
Patil, D. P. et al. m
doi: 10.1038/nature19342
Sunwoo, H. et al. Repeat E anchors Xist RNA to the inactive X chromosomal compartment through CDKN1A-interacting protein (CIZ1). Proc. Natl Acad. Sci. USA 114, 10654–10659 (2017).
doi: 10.1073/pnas.1711206114
Jeon, Y. & Lee, J. T. YY1 tethers Xist RNA to the inactive X nucleation center. Cell 146, 119–133 (2011).
doi: 10.1016/j.cell.2011.06.026
Colognori, D. et al. Xist deletional analysis reveals an interdependency between Xist RNA and polycomb complexes for spreading along the inactive X. Mol. Cell 74, 101–117 e110 (2019).
doi: 10.1016/j.molcel.2019.01.015
Liu, F. et al. Visualizing the secondary and tertiary architectural domains of lncRNA RepA. Nat. Chem. Biol. 13, 282–289 (2017).
doi: 10.1038/nchembio.2272
Kikhney, A. G. & Svergun, D. I. A practical guide to small angle X-ray scattering (SAXS) of flexible and intrinsically disordered proteins. FEBS Lett. 589, 2570–2577 (2015).
doi: 10.1016/j.febslet.2015.08.027
Kim, D. N. et al. Zinc-finger protein CNBP alters the 3-D structure of lncRNA Braveheart in solution. Nat. Commun. 11, 148 (2020).
doi: 10.1038/s41467-019-13942-4
Carrette, L. L. G. et al. A mixed modality approach towards Xi reactivation for Rett syndrome and other X-linked disorders. Proc. Natl Acad. Sci. USA 115, 1715124115 (2017).
Stelzer, A. C. et al. Discovery of selective bioactive small molecules by targeting an RNA dynamic ensemble. Nat. Chem. Biol. 7, 553–559 (2011).
doi: 10.1038/nchembio.596

Auteurs

Rodrigo Aguilar (R)

Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Institute of Biomedical Sciences (ICB), Faculty of Medicine and Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile.

Kerrie B Spencer (KB)

Merck & Co., Boston, MA, USA.

Barry Kesner (B)

Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA, USA.

Noreen F Rizvi (NF)

Merck & Co., Boston, MA, USA.

Maulik D Badmalia (MD)

Alberta RNA Research and Training Institute, Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Alberta, Canada.

Tyler Mrozowich (T)

Alberta RNA Research and Training Institute, Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Alberta, Canada.

Jonathan D Mortison (JD)

Merck & Co., Boston, MA, USA.

Carlos Rivera (C)

Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA, USA.

Graham F Smith (GF)

Merck & Co., Boston, MA, USA.

Julja Burchard (J)

Merck & Co., Boston, MA, USA.

Peter J Dandliker (PJ)

Merck & Co., Boston, MA, USA.

Trushar R Patel (TR)

Alberta RNA Research and Training Institute, Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Alberta, Canada.

Elliott B Nickbarg (EB)

Merck & Co., Boston, MA, USA.

Jeannie T Lee (JT)

Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA. lee@molbio.mgh.harvard.edu.
Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA, USA. lee@molbio.mgh.harvard.edu.

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