Mutually Exclusive CBC-Containing Complexes Contribute to RNA Fate

Simone Giacometti, Nour El Houda Benbahouche, Michal Domanski, Marie Cécile Robert, Nicola Meola, Michal Lubas, Jakob Bukenborg, Jens S. Andersen, Wiebke M. Schulze, Celine Verheggen, Grzegorz Kudla*, Torben Heick Jensen, Edouard Bertrand

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

The nuclear cap-binding complex (CBC) stimulates processing reactions of capped RNAs, including their splicing, 3′-end formation, degradation, and transport. CBC effects are particular for individual RNA families, but how such selectivity is achieved remains elusive. Here, we analyze three main CBC partners known to impact different RNA species. ARS2 stimulates 3′-end formation/transcription termination of several transcript types, ZC3H18 stimulates degradation of a diverse set of RNAs, and PHAX functions in pre-small nuclear RNA/small nucleolar RNA (pre-snRNA/snoRNA) transport. Surprisingly, these proteins all bind capped RNAs without strong preferences for given transcripts, and their steady-state binding correlates poorly with their function. Despite this, PHAX and ZC3H18 compete for CBC binding and we demonstrate that this competitive binding is functionally relevant. We further show that CBC-containing complexes are short lived in vivo, and we therefore suggest that RNA fate involves the transient formation of mutually exclusive CBC complexes, which may only be consequential at particular checkpoints during RNA biogenesis.

Original languageEnglish
JournalCell Reports
Volume18
Issue number11
Pages (from-to)2635-2650
ISSN2211-1247
DOIs
Publication statusPublished - 2017

Keywords

  • cap
  • CBC
  • CBC interacting proteins
  • CLIP
  • FRAP
  • RNA cap
  • RNA decay
  • RNA fate decisions
  • RNA transport

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