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Mammalian RNA Decay Pathways Are Highly Specialized and Widely Linked to Translation.

  • 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.
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  • 2020-02-13
Published in:
  • Molecular cell. - 2020
AVEN
RNA
RNA decay
RNA degradation
RNA surveillance
SKIV2L
histones
ribosome
ribosome stalling
translation
Animals
Apoptosis Regulatory Proteins
CRISPR-Cas Systems
DNA-Binding Proteins
Exoribonucleases
Gene Expression Regulation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mouse Embryonic Stem Cells
Open Reading Frames
Protein Biosynthesis
Proto-Oncogene Proteins
RNA Helicases
RNA Stability
RNA, Messenger
Ribosomes
English 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.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/92577
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