scholarly journals Spliced‐leader RNA silencing: a novel stress‐induced mechanism in Trypanosoma brucei

EMBO Reports ◽  
2007 ◽  
Vol 8 (4) ◽  
pp. 408-413 ◽  
Author(s):  
Yaniv Lustig ◽  
Lilach Sheiner ◽  
Yaron Vagima ◽  
Hanoch Goldshmidt ◽  
Anish Das ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Rna Silencing ◽  
Spliced Leader ◽  
Spliced Leader Rna

scholarly journals The spliced leader RNA silencing (SLS) pathway in Trypanosoma brucei is induced by perturbations of endoplasmic reticulum, Golgi, or mitochondrial proteins factors and functional analysis of SLS inducing kinase, PK3

2021 ◽  
Author(s):  
Uthman Okalang ◽  
Bar Mualem Bar-Ner ◽  
K. Shanmugha Rajan ◽  
Nehemya Friedman ◽  
Saurav Aryal ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Trypanosoma Brucei ◽  
Rna Silencing ◽  
Protein Import ◽  
Protein Translocation ◽  
Mitochondrial Protein ◽  
Serine Threonine Kinase ◽  
Spliced Leader ◽  
Quiescin Sulfhydryl Oxidase ◽  
Spliced Leader Rna

ABSTRACTIn the parasite Trypanosoma brucei, the causative agent of human African sleeping sickness, all mRNAs are trans-spliced to generate a common 5’ exon derived from the spliced leader RNA (SL RNA). Perturbations of protein translocation across the endoplasmic reticulum (ER) induce the spliced leader RNA silencing (SLS) pathway. SLS activation is mediated by a serine-threonine kinase, PK3, which translocates from the cytosolic face of the ER to the nucleus, where it phosphorylates the TATA binding protein TRF4, leading to the shut-off of SL RNA transcription, followed by induction of programmed cell death. Here, we demonstrate that SLS is also induced by depletion of the essential ER resident chaperones BiP and calreticulin, ER oxidoreductin 1 (ERO1), and the Golgi-localized quiescin sulfhydryl oxidase (QSOX1). Most strikingly, silencing of Rhomboid-like 1(TIMRHOM1) involved in mitochondrial protein import, also induces SLS. The PK3 kinase, which integrates SLS signals, is modified by phosphorylation on multiple sites. To determine which of the phosphorylation events activate PK3, several individual mutations or their combination were generated. These mutations failed to completely eliminate the phosphorylation or translocation of the kinase to the nucleus. The structure of PK3 kinase and its ATP binding domain were therefore modeled. A conserved phenylalanine at position 771 was proposed to interact with ATP, and the PK3F771L mutation completely eliminated phosphorylation under SLS, suggesting that the activation involves most if not all the phosphorylation sites. The study suggests that the SLS occurs broadly in response to failures in protein sorting, folding, or modification across multiple compartments.

scholarly journals Persistent ER Stress Induces the Spliced Leader RNA Silencing Pathway (SLS), Leading to Programmed Cell Death in Trypanosoma brucei

2010 ◽  
Vol 6 (1) ◽  
pp. e1000731 ◽  
Author(s):  
Hanoch Goldshmidt ◽  
Devorah Matas ◽  
Anat Kabi ◽  
Shai Carmi ◽  
Ronen Hope ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Er Stress ◽  
Trypanosoma Brucei ◽  
Rna Silencing ◽  
Spliced Leader ◽  
Spliced Leader Rna

scholarly journals The nuclear RNA binding protein RBP33 influences mRNA and spliced leader RNA abundance in Trypanosoma brucei

2017 ◽  
Vol 212 ◽  
pp. 16-20 ◽  
Author(s):  
Olivera Cirovic ◽  
Roman Trikin ◽  
Anneliese Hoffmann ◽  
Nicholas Doiron ◽  
Martin Jakob ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Spliced Leader ◽  
Nuclear Rna ◽  
Spliced Leader Rna
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