An evolutionarily conserved RNA structure in the functional core of the lincRNA Cyrano.


Journal

RNA (New York, N.Y.)
ISSN: 1469-9001
Titre abrégé: RNA
Pays: United States
ID NLM: 9509184

Informations de publication

Date de publication:
09 2020
Historique:
received: 27 04 2020
accepted: 18 05 2020
pubmed: 28 5 2020
medline: 6 10 2020
entrez: 28 5 2020
Statut: ppublish

Résumé

The wide prevalence and regulated expression of long noncoding RNAs (lncRNAs) highlight their functional roles, but the molecular basis for their activities and structure-function relationships remains to be investigated, with few exceptions. Among the relatively few lncRNAs conserved over significant evolutionary distances is the long intergenic noncoding RNA (lincRNA) Cyrano (orthologous to human OIP5-AS1), which contains a region of 300 highly conserved nucleotides within tetrapods, which in turn contains a functional stretch of 26 nt of deep conservation. This region binds to and facilitates the degradation of the microRNA miR-7, a short ncRNA with multiple cellular functions, including modulation of oncogenic expression. We probed the secondary structure of Cyrano in vitro and in cells using chemical and enzymatic probing, and validated the results using comparative sequence analysis. At the center of the functional core of Cyrano is a cloverleaf structure maintained over the >400 million years of divergent evolution that separates fish and primates. This strikingly conserved motif provides interaction sites for several RNA-binding proteins and masks a conserved recognition site for miR-7. Conservation in this region strongly suggests that the function of Cyrano depends on the formation of this RNA structure, which could modulate the rate and efficiency of degradation of miR-7.

Identifiants

pubmed: 32457084
pii: rna.076117.120
doi: 10.1261/rna.076117.120
pmc: PMC7430676
doi:

Substances chimiques

MicroRNAs 0
RNA, Long Noncoding 0
RNA, Messenger 0
RNA, Untranslated 0
RNA-Binding Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1234-1246

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM103834
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM121487
Pays : United States
Organisme : NIGMS NIH HHS
ID : R25 GM086304
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM126942
Pays : United States

Informations de copyright

© 2020 Jones et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

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Auteurs

Alisha N Jones (AN)

Department of Chemistry, University of Washington, Box 351700, Seattle, Washington 98195, USA.

Giuseppina Pisignano (G)

Department of Chemistry, University of Washington, Box 351700, Seattle, Washington 98195, USA.
Tumor Biology and Experimental Therapeutics Program, Institute of Oncology Research (IOR) and Oncology Institute of Southern Switzerland (IOSI), Bellinzona CH-6500, Switzerland.
Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom.

Thomas Pavelitz (T)

Department of Chemistry, University of Washington, Box 351700, Seattle, Washington 98195, USA.

Jessica White (J)

Department of Chemistry, University of Washington, Box 351700, Seattle, Washington 98195, USA.

Martin Kinisu (M)

Department of Chemistry, University of Washington, Box 351700, Seattle, Washington 98195, USA.

Nicholas Forino (N)

Department of Chemistry, University of Washington, Box 351700, Seattle, Washington 98195, USA.

Dreycey Albin (D)

Department of Chemistry, University of Washington, Box 351700, Seattle, Washington 98195, USA.

Gabriele Varani (G)

Department of Chemistry, University of Washington, Box 351700, Seattle, Washington 98195, USA.

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