title: PAPERCLIP Identifies MicroRNA Targets and a Role of CstF64/64tau in Promoting Non-canonical poly(A) Site Usage.
abstract: Accurate and precise annotation of 3' UTRs is critical for understanding how mRNAs are regulated by microRNAs (miRNAs) and RNA-binding proteins (RBPs). Here, we describe a method, poly(A) binding protein-mediated mRNA 3' end retrieval by crosslinking immunoprecipitation (PAPERCLIP), that shows high specificity for mRNA 3' ends and compares favorably with existing 3' end mapping methods. PAPERCLIP uncovers a previously unrecognized role of CstF64/64tau in promoting the usage of a selected group of non-canonical poly(A) sites, the majority of which contain a downstream GUKKU motif. Furthermore, in the mouse brain, PAPERCLIP discovers extended 3' UTR sequences harboring functional miRNA binding sites and reveals developmentally regulated APA shifts, including one in Atp2b2 that is evolutionarily conserved in humans and results in the gain of a functional binding site of miR-137. PAPERCLIP provides a powerful tool to decipher post-transcriptional regulation of mRNAs through APA in vivo.
authors.affiliation: Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA. Electronic address: hhwang@rockefeller.edu.
authors.forename: Hun-Way
authors.initials: HW
authors.lastname: Hwang
authors.affiliation: Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA; New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA.
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Park
authors.affiliation: Laboratory of Systems Cancer Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Hani
authors.initials: H
authors.lastname: Goodarzi
authors.affiliation: Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Fak
authors.affiliation: Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Aldo
authors.initials: A
authors.lastname: Mele
authors.affiliation: Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Moore
authors.affiliation: Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA; New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA. Electronic address: darnelr@rockefeller.edu.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Darnell
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D017124:Conserved Sequence; D019143:Evolution, Molecular; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D059372:Nucleotide Motifs / Q000235:genetics; D011061:Poly A / Q000378:metabolism*; D026723:Polyadenylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger; D016875:tau Proteins; D011061:Poly A