NCBP3 positively impacts mRNA biogenesis

Yuhui Dou (1) , Isabelle Barbosa (2) , Hua Jiang , Claudia Iasillo , Kelly Molloy , Wiebke Manuela Schulze (3) , Stephen Cusack (3) , Manfred Schmid , Hervé Le Hir (2) , John Lacava (4) , Torben Heick Jensen (1)

1 Aarhus University [Aarhus]
2 IBENS - Institut de biologie de l'ENS Paris
3 EMBL - European Molecular Biology Laboratory [Grenoble]
4 Laboratory of Molecular Biology and Biochemistry, The Rockefeller University

The nuclear Cap-Binding Complex (CBC), consisting of Nuclear Cap-Binding Protein 1 (NCBP1) and 2 (NCBP2), associates with the nascent 5 cap of RNA polymerase II transcripts and impacts RNA fate decisions. Recently, the C17orf85 protein, also called NCBP3, was suggested to form an alternative CBC by replacing NCBP2. However, applying protein-protein interaction screening of NCBP1, 2 and 3, we find that the interaction profile of NCBP3 is distinct. Whereas NCBP1 and 2 identify known CBC interactors, NCBP3 primarily interacts with components of the Exon Junction Complex (EJC) and the TRanscription and EXport (TREX) complex. NCBP3-EJC association in vitro and in vivo requires EJC core integrity and the in vivo RNA binding profiles of EJC and NCBP3 overlap. We further show that NCBP3 competes with the RNA degradation factor ZC3H18 for binding CBCbound transcripts, and that NCBP3 positively impacts the nuclear export of polyadenylated RNAs and the expression of large multi-exonic transcripts. Collectively, our results place NCBP3 with the EJC and TREX complexes in supporting mRNA expression.

Domaines: Sciences du Vivant [q-bio]

Yuhui Dou, Isabelle Barbosa, Hua Jiang, Claudia Iasillo, Kelly Molloy, et al.. NCBP3 positively impacts mRNA biogenesis. Nucleic Acids Research, 2020, 48 (18), pp.10413-10427. ⟨10.1093/nar/gkaa744⟩. ⟨hal-03033173⟩