Spliced-leader RNA silencing: a novel stress-induced mechanism in Trypanosoma brucei.
The signal-recognition particle (SRP) mediates the translocation of membrane and secretory proteins across the endoplasmic reticulum upon interaction with the SRP receptor. In trypanosomes, the main RNA molecule is the spliced-leader (SL) RNA, which donates the SL sequence to all messenger RNA through trans-splicing. Here, we show that RNA interference silencing of the SRP receptor (SRalpha) in Trypanosoma brucei caused the accumulation of SRP on ribosomes and triggered silencing of SL RNA (SLS). SLS was elicited due to the failure of the SL RNA-specific transcription factor tSNAP42 to bind to its promoter. SL RNA reduction, in turn, eliminated mRNA processing and resulted in a significant reduction of all mRNA tested. SLS was also induced under pH stress and might function as a master regulator in trypanosomes. SLS is reminiscent of, but distinct from, the unfolded protein response and can potentially act as a new target for parasite eradication.
Lustig
Yaniv
Y
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
Sheiner
Lilach
L
Vagima
Yaron
Y
Goldshmidt
Hanoch
H
Das
Anish
A
Bellofatto
Vivian
V
Michaeli
Shulamit
S
D000818:Animals; D006863:Hydrogen-Ion Concentration; D011401:Promoter Regions, Genetic; D015800:Protozoan Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D020038:RNA, Spliced Leader / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000737:chemistry / Q000235:genetics / Q000254:growth & development*
D015800:Protozoan Proteins; D012333:RNA, Messenger; D020038:RNA, Spliced Leader; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D014157:Transcription Factors; C036318:signal peptide receptor