2009-04-21

53# Stalder et al. 2008 review- NMD

Model for PTC recognition. (a) The mRNP is thought to form a closed-loop structure through the interaction of cap-bound eIF4E or CBC (for ‘‘cap-binding complex’’) with eIF4G, which in turn interacts with the poly(A) tail-bound PABPC1. When the ribosome terminates at a TC in the vicinity of the poly(A) tail, a PABPC1-mediated signal promotes proper termination of translation, resulting in efficient reinitiation of the ribosome at the 50 end of the mRNA, and the production of a stable mRNP. (b) If the ribosome terminates at a TC that is too far away from the poly(A) tail for it receive the PABPC1-mediated translation-termination-promoting signal, UPF1 binds to the stalled ribosome instead, thereby marking this TC as premature. Subsequently, UPF2 and UPF3b interact with UPF1, promoting SMG1-mediated phosphorylation of UPF1. This licensing step commits the mRNA to rapid degradation by as yet unknown pathways that involve the binding of SMG5–7 to the phosphorylated UPF1 (upper part). An EJC downstream of a TC functions as an NMD enhancer by shortening the time window between UPF1 binding and its
phosphorylation by locally concentrating UPF2 and UPF3b (lower part).

50#Wilson et al. 2008 review BBC-cytoplasmic mRNA surveillance pathways

normal mRNA degradation

nonstop mRNA degradation

no-go mRNA decay

unspliced and partially spliced mRNAs

54# Sheth et al. 2006Cell-P bodies

model for the process of nonsense-mediated-decay

55# Parker et al. 2007reviewMol Cell-P bodies

mRNA degradation