Abstract:
:Liu and Mertz (Genes Dev. 9:1766-1780, 1995) previously identified a 119-nt pre-mRNA processing enhancer (PPE) element within the herpes simplex virus type 1 thymidine kinase gene that enables intron-independent gene expression in higher eukaryotes by binding heterogeneous nuclear ribonucleoprotein L (hnRNP L). Here, we identify a 49-nt subelement within this PPE that enhanced stability, polyadenylation, and cytoplasmic accumulation of transcripts synthesized in CV-1 cells from an intronless variant of the human beta-globin gene when present in two or more tandem copies. This 2xTK49 PPE also enhanced (i) the efficiency of polyadenylation of intronless beta-globin RNA in a cell-free polyadenylation system and (ii) the kinetics of nucleocytoplasmic export of an intronless variant of adenovirus major late leader region RNA in Xenopus oocytes. This 2xTK49 PPE bound only hnRNP L. Analysis of 2xTK49 PPE mutants showed a strong positive correlation existed between binding hnRNP L and enhancement of intronless beta-globin gene expression. hnRNP L was found to associate with both the mRNA export factor TAP and the exon-exon junction complex protein Aly/REF. Thus, we conclude that hnRNP L plays roles in enhancing stability, polyadenylation, and nucleocytoplasmic export; it does so, at least in part, by directly recruiting to intronless PPE-containing RNAs cofactors normally recruited to intron-containing RNAs.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Guang S,Felthauser AM,Mertz JEdoi
10.1128/MCB.25.15.6303-6313.2005subject
Has Abstractpub_date
2005-08-01 00:00:00pages
6303-13issue
15eissn
0270-7306issn
1098-5549pii
25/15/6303journal_volume
25pub_type
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