Chtop (Chromatin target of Prmt1) auto-regulates its expression level via intron retention and nonsense-mediated decay of its own mRNA

摘要: Chtop (chromatin target of Prmt1) regulates various aspects gene expression including transcription and mRNA export. Despite these important functions, the regulatory mechanism underlying remains undetermined. Using Chtop-expressing human cell lines, we demonstrate that is controlled via an autoregulatory negative feedback loop whereby binds its own to retain intron 2 during splicing; a premature termination codon present at 5' end leads nonsense-mediated decay mRNA. We also show interacts with exon arginine-glycine-rich (RG) domain, N-terminal (N1) domain; both are required for retention 2. In addition, hnRNP H accelerates splicing in manner dependent on level, suggesting regulate antagonistically. Thus, study provides novel molecular by which protein levels constitutively regulated retention.