title: Overlapping and distinct functions of CstF64 and CstF64τ in mammalian mRNA 3' processing.
abstract: mRNA 3' processing is dynamically regulated spatially and temporally. However, the underlying mechanisms remain poorly understood. CstF64τ is a paralog of the general mRNA 3' processing factor, CstF64, and has been implicated in mediating testis-specific mRNA alternative polyadenylation (APA). However, the functions of CstF64τ in mRNA 3' processing have not been systematically investigated. We carried out a comprehensive characterization of CstF64τ and compared its properties to those of CstF64. In contrast to previous reports, we found that both CstF64 and CstF64τ are widely expressed in mammalian tissues, and their protein levels display tissue-specific variations. We further demonstrated that CstF64 and CstF64τ have highly similar RNA-binding specificities both in vitro and in vivo. CstF64 and CstF64τ modulate one another's expression and play overlapping as well as distinct roles in regulating global APA profiles. Interestingly, protein interactome analyses revealed key differences between CstF64 and CstF64τ, including their interactions with another mRNA 3' processing factor, symplekin. Together, our study of CstF64 and CstF64τ revealed both functional overlap and specificity of these two important mRNA 3' processing factors and provided new insights into the regulatory mechanisms of mRNA 3' processing.
authors.forename: Chengguo
authors.initials: C
authors.lastname: Yao
authors.forename: Eun-A
authors.initials: EA
authors.lastname: Choi
authors.forename: Lingjie
authors.initials: L
authors.lastname: Weng
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xie
authors.forename: Ji
authors.initials: J
authors.lastname: Wan
authors.forename: Yi
authors.initials: Y
authors.lastname: Xing
authors.forename: James J
authors.initials: JJ
authors.lastname: Moresco
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Tu
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D039241:Cleavage Stimulation Factor; D016384:Consensus Sequence; D015870:Gene Expression; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D026723:Polyadenylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*
chemical_list: C474466:CSTF2T protein, human; D039241:Cleavage Stimulation Factor; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C101043:SYMPK protein, human
keywords: 3′ end formation; alternative polyadenylation; mRNA processing; sequencing