Abstract：
:Nonsense-mediated decay (NMD) degrades mRNAs containing a premature termination codon (PTC). PTCs are a frequent cause of human genetic diseases, and the NMD pathway is known to modulate disease severity. Since partial NMD attenuation can potentially enhance nonsense suppression therapies, better definition of human-specific NMD is required. However, the majority of NMD factors were first discovered in model organisms and then subsequently identified by homology in human. Sensitivity and throughput limitations of existing approaches have hindered systematic forward genetic screening for NMD factors in human cells. We developed a method of in vivo amplification of NMD reporter fluorescence (Fireworks) that enables CRISPR-based forward genetic screening for NMD pathway defects in human cells. The Fireworks genetic screen identifies multiple known NMD factors and numerous human candidate genes, providing a platform for discovery of additional key factors in human mRNA degradation.
journal_name
Mol Celljournal_title
Molecular cellauthors
Alexandrov A,Shu MD,Steitz JAdoi
10.1016/j.molcel.2016.11.032subject
Has Abstractpub_date
2017-01-05 00:00:00pages
191-201issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(16)30777-8journal_volume
65pub_type
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