title: Nucleophosmin deposition during mRNA 3' end processing influences poly(A) tail length.
abstract: During polyadenylation, the multi-functional protein nucleophosmin (NPM1) is deposited onto all cellular mRNAs analysed to date. Premature termination of poly(A) tail synthesis in the presence of cordycepin abrogates deposition of the protein onto the mRNA, indicating natural termination of poly(A) addition is required for NPM1 binding. NPM1 appears to be a bona fide member of the complex involved in 3' end processing as it is associated with the AAUAAA-binding CPSF factor and can be co-immunoprecipitated with other polyadenylation factors. Furthermore, reduction in the levels of NPM1 results in hyperadenylation of mRNAs, consistent with alterations in poly(A) tail chain termination. Finally, knockdown of NPM1 results in retention of poly(A)(+) RNAs in the cell nucleus, indicating that NPM1 influences mRNA export. Collectively, these data suggest that NPM1 has an important role in poly(A) tail length determination and may help network 3' end processing with other aspects of nuclear mRNA maturation.
authors.affiliation: Cell and Molecular Biology Graduate Program, Colorado State University, Fort Collins, CO, USA.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sagawa
authors.forename: Hend
authors.initials: H
authors.lastname: Ibrahim
authors.forename: Angela L
authors.initials: AL
authors.lastname: Morrison
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Wilusz
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wilusz
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D010957:Plasmids / Q000378:metabolism; D011061:Poly A / Q000235:genetics*; D026723:Polyadenylation; D012333:RNA, Messenger / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D039221:mRNA Cleavage and Polyadenylation Factors; D000090243:Nucleophosmin; D011061:Poly A