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Sci Signal. 2014 Sep 2;7(341):ra85. doi: 10.1126/scisignal.2005234.

Phosphorylation of the TATA-binding protein activates the spliced leader silencing pathway in Trypanosoma brucei.

Author information

1
The Mina and Everard Goodman Faculty of Life Sciences, and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 52900, Israel.
2
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
3
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.

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.

PMID:
25185157
DOI:
10.1126/scisignal.2005234
[Indexed for MEDLINE]

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