title: Cleavage factor Im is a key regulator of 3' UTR length.
abstract: In eukaryotes, the 3' ends of RNA polymerase II-transcribed RNAs are generated in the majority of cases by site-specific endonucleolytic cleavage, followed by the addition of a poly(A) tail. Through alternative polyadenylation, a gene can give rise to multiple mRNA isoforms that differ in the length of their 3' UTRs and hence in their susceptibility to post-transcriptional regulatory factors such as microRNAs. A series of recently conducted high-throughput studies of poly(A) site usage revealed an extensive tissue-specific control and drastic changes in the length of mRNA 3' UTRs upon induction of proliferation in resting cells. To understand the dynamics of poly(A) site choice, we recently identified binding sites of the major pre-mRNA 3' end processing factors - cleavage and polyadenylation specificity factor (CPSF), cleavage stimulation factor (CstF), and cleavage factor Im (CF Im) - and mapped polyadenylation sites in HEK293 cells. Our present study extends previous findings on the role of CF Im in alternative polyadenylation and reveals that subunits of the CF Im complex generally control 3' UTR length. More specifically, we demonstrate that the loss-of-function of CF Im 68 and CF Im 25 but not of CF Im 59 leads to a transcriptome-wide increase in the use of proximal polyadenylation sites in HEK293 cells.
authors.affiliation: Biozentrumm, University of Basel and Swiss Institute of Bioinformatics, Basel, Switzerland.
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Gruber
authors.forename: Georges
authors.initials: G
authors.lastname: Martin
authors.forename: Walter
authors.initials: W
authors.lastname: Keller
authors.forename: Mihaiela
authors.initials: M
authors.lastname: Zavolan
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D049109:Cell Proliferation; D039241:Cleavage Stimulation Factor; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D026723:Polyadenylation; D025941:Protein Interaction Mapping; D059367:RNA Cleavage; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C474466:CSTF2T protein, human; D039241:Cleavage Stimulation Factor; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C450562:cleavage factor Im, human; D039221:mRNA Cleavage and Polyadenylation Factors