Open AccessPTC readthrough in human cells occurs in novel cytoplasmic foci and requires UPF proteins
Author(s) -
Jinchao Jia,
Elisabeth Werkmeister,
Sara Gonzalez-Hilarion,
Catherine Leroy,
Dieter C. Gruenert,
Frank Lafont,
David Tulasne,
Fabrice Lejeune
Publication year - 2017
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.198176
Subject(s) - biology , nonsense mediated decay , cytoplasm , microbiology and biotechnology , ribonucleoprotein , nonsense mutation , microtubule , cytoskeleton , messenger rnp , messenger rna , mutation , genetics , gene , rna , cell , rna splicing , missense mutation
Nonsense-mutation-containing messenger ribonucleoprotein particles (mRNPs) transit through cytoplasmic foci called P-bodies before undergoing nonsense-mediated mRNA decay (NMD), a cytoplasmic mRNA surveillance mechanism. This study shows that the cytoskeleton modulates transport of nonsense-mutation-containing mRNPs to and from P-bodies. Impairing the integrity of cytoskeleton causes inhibition of NMD. The cytoskeleton thus plays a crucial role in NMD. Interestingly, disruption of actin filaments results in both inhibition of NMD and activation of readthrough, while disruption of microtubules causes only NMD inhibition. Activation of readthrough occurs concomitantly with the appearance of cytoplasmic foci containing UPF proteins and mRNAs with nonsense mutations but lacking the P-body marker DCP1a. These findings demonstrate that in human cells, readthrough occurs in novel “readthrough bodies” and requires the presence of UPF proteins.