mRNP Rearrangements During the Pioneer Round of Translation, Nonsense- Mediated mRNA Decay, and Thereafter
Lynne Maquat
Department of Biochemistry and Biophysics and the Center for RNA Biology
School of Medicine and Dentistry, University of Rochester
coauthors: Jungwook Hwang, Hanae Sato, Chenguang Gong, Yalan Tang
In mammalian cells, two different messenger ribonucleoproteins (mRNPs) serve as templates
for protein synthesis. Newly synthesized CBP80/CBP20-bound mRNPs initially undergo
a pioneer round of translation (Maquat et al., 2010). One purpose
of this round of translation is to ensure the quality of
gene expression, as exemplified by nonsense-mediated mRNA decay (NMD). NMD
largely functions to eliminate mRNAs that prematurely terminate translation, although NMD
also contributes to proper gene control, and it targets CBP80/CBP20-
bound mRNPs (for recent publications, see Sato et al., 2008; Isken
et al., 2008). CBP80/CBP20-bound mRNPs are remodeled to eIF4E-
bound mRNPs as a consequence of the pioneer round of translation
as well as independently of translation (Sato and Maquat, 2009). eIF4E-
bound mRNPs support the bulk of cellular protein synthesis and are
the primary targets of mRNA decay mechanisms that conditionally regulate gene
expression, such as Staufen1-mediated mRNA decay (see, e.g., Gong
et al., 2009). Mechanistic aspects of NMD will be discussed, including
how CBP80, which is acquired by the 5 caps of newly
synthesized transcripts within nuclei, promotes NMD at multiple steps by promoting
specific mRNP rearrangements (Hwang et al., 2010).
Gong, C., Kim, Y.K., Woeller, C.F., Tang, Y. and
Maquat, L.E. (2009) SMD and NMD are competitive pathways that
contribute to myogenesis: Effects on PAX3 and myogenin mRNAs. Genes & Dev. 23:54-66.
Hwang, H., Sato, H., Tang, Y., Matsuda, D. and Maquat, L.
E. (2010) UPF1 association with the cap-binding protein, CBP80, promotes
nonsense-mediated mRNA decay at two distinct steps. Mol. Cell 39:396-409.
Isken, O., Kim, Y.K., Hosoda, N., Mayeur, G.L., Hershey,
J.W.B. and Maquat, L.E. (2008) Upf 1 phosphorylation
triggers translational repression during nonsense-mediated mRNA decay. Cell 133:314-
327.
Maquat, L.E., Tarn, Y.-W. and Isken, O. (2010) Specialized
features and functions of the pioneer round of translation. Cell, 142:
368-374.
Sato, H., Hosoda, N. and Maquat, L.E. (2008) Efficiency of
the pioneer round of translation affects the cellular site of nonsense-
mediated mRNA decay. Mol. Cell 29:255-262.
Sato, H. and Maquat, L.E. (2009) Remodeling of the pioneer
translation initiation complex involves translation and the karyopherin importin Genes & Dev.
23:2537-50.