Discovery and Characterization of a Eukaryotic Initiation Factor 4A-3-Selective Inhibitor That Suppresses Nonsense-Mediated mRNA Decay

2017 ◽  
Vol 12 (7) ◽  
pp. 1760-1768 ◽  
Author(s):  
Misa Iwatani-Yoshihara ◽  
Masahiro Ito ◽  
Yoshihiro Ishibashi ◽  
Hideyuki Oki ◽  
Toshio Tanaka ◽  
...  
Keyword(s):  
Mrna Decay ◽  
Selective Inhibitor ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Nonsense Mediated Mrna Decay

scholarly journals Inhibition of Nonsense-mediated mRNA Decay by the Natural Product Pateamine A through Eukaryotic Initiation Factor 4AIII

2009 ◽  
Vol 284 (35) ◽  
pp. 23613-23621 ◽  
Author(s):  
Yongjun Dang ◽  
Woon-Kai Low ◽  
Jing Xu ◽  
Niels H. Gehring ◽  
Harry C. Dietz ◽  
...  
Keyword(s):  
Natural Product ◽  
Mrna Decay ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Nonsense Mediated Mrna Decay ◽  
Pateamine A

scholarly journals Characterization of eukaryotic initiation factor 4A, a protein involved in ATP-dependent binding of globin mRNA.

1982 ◽  
Vol 257 (9) ◽  
pp. 5246-5252 ◽  
Author(s):  
J A Grifo ◽  
S M Tahara ◽  
J P Leis ◽  
M A Morgan ◽  
A J Shatkin ◽  
...  
Keyword(s):  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Globin Mrna

scholarly journals Identification and characterization of a sequence motif involved in nonsense-mediated mRNA decay.

1995 ◽  
Vol 15 (4) ◽  
pp. 2231-2244 ◽  
Author(s):  
S Zhang ◽  
M J Ruiz-Echevarria ◽  
Y Quan ◽  
S W Peltz
Keyword(s):  
Mrna Decay ◽  
Sequence Motif ◽  
Nonsense Mutations ◽  
Stem Loop ◽  
Cis Acting ◽  
Stem Loop Structure ◽  
Nonsense Codon ◽  
Nonsense Mediated Mrna Decay

In both prokaryotes and eukaryotes, nonsense mutations in a gene can enhance the decay rate or reduce the abundance of the mRNA transcribed from that gene, and we call this process nonsense-mediated mRNA decay. We have been investigating the cis-acting sequences involved in this decay pathway. Previous experiments have demonstrated that, in addition to a nonsense codon, specific sequences 3' of a nonsense mutation, which have been defined as downstream elements, are required for mRNA destabilization. The results presented here identify a sequence motif (TGYYGATGYYYYY, where Y stands for either T or C) that can predict regions in genes that, when positioned 3' of a nonsense codon, promote rapid decay of its mRNA. Sequences harboring two copies of the motif from five regions in the PGK1, ADE3, and HIS4 genes were able to function as downstream elements. In addition, four copies of this motif can function as an independent downstream element. The sequences flanking the motif played a more significant role in modulating its activity when fewer copies of the sequence motif were present. Our results indicate the sequences 5' of the motif can modulate its activity by maintaining a certain distance between the sequence motif and the termination codon. We also suggest that the sequences 3' of the motif modulate the activity of the downstream element by forming RNA secondary structures. Consistent with this view, a stem-loop structure positioned 3' of the sequence motif can enhance the activity of the downstream element. This sequence motif is one of the few elements that have been identified that can predict regions in genes that can be involved in mRNA turnover. The role of these sequences in mRNA decay is discussed.

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