Nonsense -mediated decay: A branched and regulated pathway

TL;DRAbstract

The nonsense-mediated mRNA decay (NMD) pathway is an RNA surveillance mechanism that rapidly degrades aberrant mRNAs with premature termination codons (PTCs). Recently, it has become apparent that NMD is also a posttranscriptional regulatory mechanism that regulates the expression of large subsets of normal transcripts. The physiological role of NMD in mammals is poorly understood, in part, because of the early embryonic lethality that results from complete knockout of NMD factors. To circumvent this problem, I elected to knockdown a NMD factor in Sertoli cells, a cell type not essential for mice survival that provides nutritional and functional support for male germ cells during spermatogenesis. Using a cell- and tissue-specific knockdown approach that depends on the microRNA (miRNA) pathway, I depleted the NMD factor UPF3B in mice and observed that these mice had only mild male reproductive defects. One explanation for these mild defects is that the factor that I chose to knockdown,

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