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Mammalian RNA Decay Pathways Are Highly Specialized and Widely Linked to Translation.
Tuck, Alex Charles; Rankova, Aneliya; Arpat, Alaaddin Bulak; Liechti, Luz Angelica; Hess, Daniel; Iesmantavicius, Vytautas; Castelo-Szekely, Violeta; Gatfield, David; Bühler, Marc.
Afiliação
  • Tuck AC; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
  • Rankova A; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
  • Arpat AB; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
  • Liechti LA; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
  • Hess D; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
  • Iesmantavicius V; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
  • Castelo-Szekely V; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
  • Gatfield D; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
  • Bühler M; Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Petersplatz 10, 4003 Basel, Switzerland. Electronic address: marc.buehler@fmi.ch.
Mol Cell ; 77(6): 1222-1236.e13, 2020 03 19.
Article em En | MEDLINE | ID: mdl-32048998
RNA decay is crucial for mRNA turnover and surveillance and misregulated in many diseases. This complex system is challenging to study, particularly in mammals, where it remains unclear whether decay pathways perform specialized versus redundant roles. Cytoplasmic pathways and links to translation are particularly enigmatic. By directly profiling decay factor targets and normal versus aberrant translation in mouse embryonic stem cells (mESCs), we uncovered extensive decay pathway specialization and crosstalk with translation. XRN1 (5'-3') mediates cytoplasmic bulk mRNA turnover whereas SKIV2L (3'-5') is universally recruited by ribosomes, tackling aberrant translation and sometimes modulating mRNA abundance. Further exploring translation surveillance revealed AVEN and FOCAD as SKIV2L interactors. AVEN prevents ribosome stalls at structured regions, which otherwise require SKIV2L for clearance. This pathway is crucial for histone translation, upstream open reading frame (uORF) regulation, and counteracting ribosome arrest on small ORFs. In summary, we uncovered key targets, components, and functions of mammalian RNA decay pathways and extensive coupling to translation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biossíntese de Proteínas / RNA Mensageiro / RNA Helicases / Estabilidade de RNA / Proteínas de Ligação a DNA / Proteínas Reguladoras de Apoptose / Exorribonucleases / Células-Tronco Embrionárias Murinas Limite: Animals Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biossíntese de Proteínas / RNA Mensageiro / RNA Helicases / Estabilidade de RNA / Proteínas de Ligação a DNA / Proteínas Reguladoras de Apoptose / Exorribonucleases / Células-Tronco Embrionárias Murinas Limite: Animals Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Suíça