Enhanced nucleotide chemistry and toehold nanotechnology reveals lncRNA spreading on chromatin.


Journal

Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374

Informations de publication

Date de publication:
03 2020
Historique:
received: 05 11 2019
accepted: 31 01 2020
entrez: 12 3 2020
pubmed: 12 3 2020
medline: 15 4 2020
Statut: ppublish

Résumé

Understanding the targeting and spreading patterns of long non-coding RNAs (lncRNAs) on chromatin requires a technique that can detect both high-intensity binding sites and reveal genome-wide changes in spreading patterns with high precision and confidence. Here we determine lncRNA localization using biotinylated locked nucleic acid (LNA)-containing oligonucleotides with toehold architecture capable of hybridizing to target RNA through strand-exchange reaction. During hybridization, a protecting strand competitively displaces contaminating species, leading to highly specific RNA capture of individual RNAs. Analysis of Drosophila roX2 lncRNA using this approach revealed that heat shock, unlike the unfolded protein response, leads to reduced spreading of roX2 on the X chromosome, but surprisingly also to relocalization to sites on autosomes. Our results demonstrate that this improved hybridization capture approach can reveal previously uncharacterized changes in the targeting and spreading of lncRNAs on chromatin.

Identifiants

pubmed: 32157249
doi: 10.1038/s41594-020-0390-z
pii: 10.1038/s41594-020-0390-z
doi:

Substances chimiques

Chromatin 0
Drosophila Proteins 0
Oligonucleotides 0
Pabp2 protein, Drosophila 0
RNA, Long Noncoding 0
RNA-Binding Proteins 0
locked nucleic acid 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

297-304

Subventions

Organisme : NICHD NIH HHS
ID : DP2 HD083992
Pays : United States

Commentaires et corrections

Type : ErratumIn

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Auteurs

Martin Machyna (M)

Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, USA.
Chemical Biology Institute, Yale University, West Haven, CT, USA.

Lea Kiefer (L)

Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, USA.
Chemical Biology Institute, Yale University, West Haven, CT, USA.

Matthew D Simon (MD)

Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, USA. matthew.simon@yale.edu.
Chemical Biology Institute, Yale University, West Haven, CT, USA. matthew.simon@yale.edu.

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