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Nucleophosmin is selectively deposited on mRNA during polyadenylation

Abstract

Nucleophosmin (NPM), an abundant, predominantly nucleolar protein that influences numerous cellular processes, was shown to specifically associate with the bodies of messenger RNAs as a result of the process of 3′-end formation. NPM deposition requires polyadenylation but not the 3′ cleavage event to occur on the transcript. Furthermore, the protein does not associate with RNAs bearing a preformed poly(A) tail or with mRNAs that have undergone cleavage but not polyadenylation. A region within 10 bases upstream of the AAUAAA element is required for NPM association, but deposition of the protein seems to be sequence independent. NPM association with poly(A)+ mRNAs was also demonstrated in vivo. NPM, therefore, represents a mark left on transcripts as a result of 3′-end processing and may have a role in one or more of a variety of post-transcriptional processes influenced by the polyadenylation event.

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Figure 1: A 32-kDa protein selectively associates with RNAs that have undergone polyadenylation in HeLa nuclear extracts.
Figure 2: Identification of NPM as a candidate polyadenylation mark.
Figure 3: A functional AAUAAA and the process of poly(A) addition are required for NPM association.
Figure 4: The process of polyadenylation, but not cleavage, is required for deposition of NPM on RNA substrates.
Figure 5: Sequences upstream of the AAUAAA element are required for NPM cross-linking to polyadenylated RNAs.
Figure 6: NPM is associated with poly(A)+ mRNAs in vivo.

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Acknowledgements

This work was supported by US National Institutes of Health grant GM072481 to J.W.

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Correspondence to Jeffrey Wilusz.

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Palaniswamy, V., Moraes, K., Wilusz, C. et al. Nucleophosmin is selectively deposited on mRNA during polyadenylation. Nat Struct Mol Biol 13, 429–435 (2006). https://doi.org/10.1038/nsmb1080

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