西亚试剂：A cell type–restricted mRNA surveillance pathway triggered

A cell type–restricted mRNA surveillance pathway triggered by ribosome extension into the 3' untranslated region

Jian Kong & Stephen A Liebhaber

Department of Genetics and Department of Medicine, University of Pennsylvania School of Medicine, 415 Curie Blvd., CRB 430, Philadelphia, Pennsylvania 19104, USA.

Correspondence should be addressed to Stephen A Liebhaber liebhabe@mail.med.upenn.edu

The accuracy of eukaryotic gene expression is monitored at multiple levels. Surveillance pathways have been identified that degrade messenger RNAs containing nonsense mutations, harboring stalled ribosomes or lacking termination codons. Here we report a previously uncharacterized surveillance pathway triggered by ribosome extension into the 3' untranslated region. This ribosome extension–mediated decay, REMD, accounts for marked repression of protein synthesis from a human -globin gene containing a prevalent antitermination mutation. REMD can be mechanistically distinguished from other surveillance pathways by its functional linkage to accelerated deadenylation, by its independence from the NMD factor Upf1 and by cell-type restriction. This unusual pathway of mRNA surveillance is likely to act as a modifier of additional genetic defects and may reflect post-transcriptional controls particular to erythroid and other differentiated cell lineages.

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