Mutually Exclusive CBC-Containing Complexes Contribute to RNA Fate

Publication date: 14 March 2017
Source:Cell Reports, Volume 18, Issue 11
Author(s): 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
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.

Graphical abstract

Teaser

The nuclear CBC plays diverse roles in RNA biogenesis and it is not clear how selective effects are achieved for individual RNA families. Giacometti et al. suggest that RNA fate involves the formation of short-lived, mutually exclusive CBC complexes, which may only be consequential at particular checkpoints during RNA biogenesis.


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