title: Phosphorylation of the TATA-binding protein activates the spliced leader silencing pathway in Trypanosoma brucei.
abstract: The parasite Trypanosoma brucei is the causative agent of human African sleeping sickness. T. brucei genes are constitutively transcribed in polycistronic units that are processed by trans-splicing and polyadenylation. All mRNAs are trans-spliced to generate mRNAs with a common 5' exon derived from the spliced leader RNA (SL RNA). Persistent endoplasmic reticulum (ER) stress induces the spliced leader silencing (SLS) pathway, which inhibits trans-splicing by silencing SL RNA transcription, and correlates with increased programmed cell death. We found that during ER stress induced by SEC63 silencing or low pH, the serine-threonine kinase PK3 translocated from the ER to the nucleus, where it phosphorylated the TATA-binding protein TRF4, leading to the dissociation of the transcription preinitiation complex from the promoter of the SL RNA encoding gene. PK3 loss of function attenuated programmed cell death induced by ER stress, suggesting that SLS may contribute to the activation of programmed cell death.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Ronen
authors.initials: R
authors.lastname: Hope
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Ben-Mayor
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Nehemya
authors.initials: N
authors.lastname: Friedman
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Voloshin
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Dipul
authors.initials: D
authors.lastname: Biswas
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Devorah
authors.initials: D
authors.lastname: Matas
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Drori
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Günzl
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel. shulamit.michaeli@biu.ac.il.
authors.forename: Shulamit
authors.initials: S
authors.lastname: Michaeli
mesh_terms: D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D005091:Exons; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006863:Hydrogen-Ion Concentration; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020038:RNA, Spliced Leader; D035181:TATA-Box Binding Protein / Q000378:metabolism*; D014158:Transcription, Genetic; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D012333:RNA, Messenger; D020038:RNA, Spliced Leader; D035181:TATA-Box Binding Protein; C000597889:PK3 protein, Trypanosoma brucei; D017346:Protein Serine-Threonine Kinases