TY - JOUR
T1 - Phosphorylation of the TATA-binding protein activates the spliced leader silencing pathway in Trypanosoma brucei
AU - Hope, Ronen
AU - Ben-Mayor, Efrat
AU - Friedman, Nehemya
AU - Voloshin, Konstantin
AU - Biswas, Dipul
AU - Matas, Devorah
AU - Drori, Yaron
AU - Günzl, Arthur
AU - Michaeli, Shulamit
N1 - Publisher Copyright:
© 2014 by the American Association for the Advancement of Science; all rights reserved.
PY - 2014/9/2
Y1 - 2014/9/2
N2 - 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. AllmRNAs 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 SLRNAencoding 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.Copyright
AB - 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. AllmRNAs 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 SLRNAencoding 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.Copyright
UR - http://www.scopus.com/inward/record.url?scp=84907575398&partnerID=8YFLogxK
U2 - 10.1126/scisignal.2005234
DO - 10.1126/scisignal.2005234
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C2 - 25185157
AN - SCOPUS:84907575398
SN - 1945-0877
VL - 7
JO - Science Signaling
JF - Science Signaling
IS - 341
M1 - ra85
ER -
