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Endogenous transcripts control miRNA levels and activity in mammalian cells by target-directed miRNA degradation.
Ghini, Francesco; Rubolino, Carmela; Climent, Montserrat; Simeone, Ines; Marzi, Matteo J; Nicassio, Francesco.
Afiliación
  • Ghini F; Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia (IIT)-Via Adamello 16, 20139, Milan, Italy.
  • Rubolino C; Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia (IIT)-Via Adamello 16, 20139, Milan, Italy.
  • Climent M; Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia (IIT)-Via Adamello 16, 20139, Milan, Italy.
  • Simeone I; Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia (IIT)-Via Adamello 16, 20139, Milan, Italy.
  • Marzi MJ; Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia (IIT)-Via Adamello 16, 20139, Milan, Italy. matteo.marzi@iit.it.
  • Nicassio F; Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia (IIT)-Via Adamello 16, 20139, Milan, Italy. francesco.nicassio@iit.it.
Nat Commun ; 9(1): 3119, 2018 08 07.
Article en En | MEDLINE | ID: mdl-30087332
Little is known about miRNA decay. A target-directed miRNA degradation mechanism (TDMD) has been suggested, but further investigation on endogenous targets is necessary. Here, we identify hundreds of targets eligible for TDMD and show that an endogenous RNA (Serpine1) controls the degradation of two miRNAs (miR-30b-5p and miR-30c-5p) in mouse fibroblasts. In our study, TDMD occurs when the target is expressed at relatively low levels, similar in range to those of its miRNAs (100-200 copies per cell), and becomes more effective at high target:miRNA ratios (>10:1). We employ CRISPR/Cas9 to delete the miR-30 responsive element within Serpine1 3'UTR and interfere with TDMD. TDMD suppression increases miR-30b/c levels and boosts their activity towards other targets, modulating gene expression and cellular phenotypes (i.e., cell cycle re-entry and apoptosis). In conclusion, a sophisticated regulatory layer of miRNA and gene expression mediated by specific endogenous targets exists in mammalian cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Serpina E2 / Fibroblastos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Serpina E2 / Fibroblastos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido