CBP80-Promoted mRNP Rearrangements during the Pioneer Round of Translation, Nonsense-Mediated mRNA Decay, and Thereafter

Abstract

In mammalian cells, two different messenger ribonucleoproteins (mRNPs) serve as templates for protein synthesis. Newly synthesized mRNPs bound by the cap-binding protein heterodimer CBP80-CBP20 (CBC) initially undergo a pioneer round of translation. One purpose of this round of translation is to ensure the quality of gene expression, as exemplified by nonsense-mediated messenger RNA (mRNA) decay (NMD). NMD largely functions to eliminate mRNAs that prematurely terminate translation, although NMD also contributes to proper gene control, and it targets CBC-bound mRNPs. CBC-bound mRNPs are remodeled to eukaryotic translation initiation factor (eIF)4E-bound mRNPs in steps that (1) are a consequence of the pioneer round of translation and (2) occur independently of translation. Rather than supporting NMD, eIF4E-bound mRNPs provide for the bulk of cellular protein synthesis and are the primary targets of mRNA decay mechanisms that conditionally regulate gene expression. Here, we overview cellular processes by which CBC-bound mRNPs are remodeled to eIF4E-bound mRNPs. We also describe the molecular movements of certain factors during NMD in view of the influential role of CBP80.

Differential Role for Host Translation Factors in Host and Viral Protein Synthesis during Human Cytomegalovirus Infection

“…Viruses that inactivate eIF4F often rely on an alternative suite of translation initiation factors (43). Host cells also utilize alternative translation initiation complexes, most notably the cap binding complex (CBC) (44). Like eIF4F, the CBC binds to the m 7 G cap and can recruit ribosomes to facilitate mRNA translation.…”

Unr defines a novel class of nucleoplasmic reticulum involved in mRNA translation

“…poly(A) RNA concentrated in the vicinity of nuclear pores and the ER, suggests that Unr-NRs are sites of active translation of newly exported mRNAs. As mRNAs exit the nucleus, they undergo a pioneer round of translation, initiated by the cap-binding complex (CBC) comprising NCBP1 and NCBP2 (Maquat et al, 2010). The CBC is then replaced by the main translation initiation factor 4E (eIF4E), which directs steady-state rounds of mRNA translation.…”

Structural insights into nonsense-mediated mRNA decay (NMD) by electron microscopy

“…NMD requires translating ribosomes and a signal downstream of the stop codon to define the context of translation termination as physiological or aberrant. The mechanistic details and specificities in each organism are a matter of debate and intense research [8][9][10][11][12][13][14][15][16]. In humans, the exon-junction-complex (EJC), four proteins assembled onto mRNA at a few nucleotides upstream of the exon-exon boundary upon splicing, is a major downstream element promoting NMD (Figure 1a).…”