Journal
EMBO JOURNAL
Volume 23, Issue 9, Pages 1968-1976Publisher
WILEY
DOI: 10.1038/sj.emboj.7600213
Keywords
hDcp2; mRNA decapping; poly(A)-binding protein; cap binding
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Funding
- NIDDK NIH HHS [DK51611, R01 DK051611] Funding Source: Medline
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Regulation of mRNA decapping is a critical determinant for gene expression. We demonstrate that the poly(A) tail-mediated regulation of mRNA decapping observed in humans can be recapitulated in vitro by the cytoplasmic poly (A)-binding protein PABP through a direct and specific binding to the 5' end of capped mRNA. The specific association of PABP with the cap occurred only within the context of the RNA whereby a cap attached to an RNA moiety served as the high-affinity substrate but not the cap structure or RNA alone. Binding of PABP to the RNA 5' end required the presence of the cap and was accentuated by the N7 methyl moiety of the cap. Interestingly, conditions that enhanced hDcp2 decapping activity reduced the affinity of PABP for cap association and consequently its ability to inhibit decapping, suggestive of a regulated association of PABP with the cap. These observations reveal a novel direct involvement of human PABP in the stabilization of mRNA by protecting the 5' end from decapping.
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