title: hALP, a novel transcriptional U three protein (t-UTP), activates RNA polymerase I transcription by binding and acetylating the upstream binding factor (UBF).
abstract: Transcription of ribosome RNA precursor (pre-rRNA) and pre-rRNA processing are coordinated by a subset of U three proteins (UTPs) known as transcriptional UTPs (t-UTPs), which participate in pre-rRNA transcription in addition to participation in 18 S rRNA processing. However, the mechanism by which t-UTPs function in pre-rRNA transcription remains undetermined. In the present study, we identified hALP, a histone acetyl-transferase as a novel t-UTP. We first showed that hALP is nucleolar, and is associated with U3 snoRNA and required for 18 S rRNA processing. Moreover, depletion of hALP resulted in a decreased level of 47 S pre-rRNA. Ectopic expression of hALP activated the rDNA promoter luciferase reporter and knockdown of hALP inhibited the reporter. In addition, hALP bound rDNA. Taken together these data identify hALP as a novel t-UTP. Immunoprecipitation and GST pulldown experiments showed that hALP binds the upstream binding factor (UBF) in vivo and in vitro. It is of importance that hALP acetylated UBF depending on HAT in vivo, and hALP but not hALP (ΔHAT) facilitated the nuclear translocation of the RNA polymerase I (Pol I)-associated factor 53 (PAF53) from the cytoplasm and promoted the association of UBF with PAF53. Thus, we provide a mechanism in which a novel t-UTP activates Pol I transcription by binding and acetylating UBF.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Kong
authors.forename: Liangliang
authors.initials: L
authors.lastname: Zhang
authors.forename: Lelin
authors.initials: L
authors.lastname: Hu
authors.forename: Qunhui
authors.initials: Q
authors.lastname: Peng
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Du
authors.forename: Yang
authors.initials: Y
authors.lastname: Ke
mesh_terms: D000107:Acetylation; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D001215:Asparaginase / Q000235:genetics / Q000378:metabolism*; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D010957:Plasmids / Q000235:genetics; D035463:Pol1 Transcription Initiation Complex Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D012318:RNA Polymerase I / Q000235:genetics / Q000378:metabolism*; D012337:RNA, Ribosomal, 18S / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D020537:RNA, Small Nucleolar / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D001324:Autoantigens; C099638:POLR1E protein, human; D035463:Pol1 Transcription Initiation Complex Proteins; D012337:RNA, Ribosomal, 18S; D034741:RNA, Small Interfering; D020537:RNA, Small Nucleolar; C117378:RNA, U3 small nucleolar; D014157:Transcription Factors; C063844:transcription factor UBF; D012318:RNA Polymerase I; C466840:ASRGL1 protein, human; D001215:Asparaginase