Spliced-leader RNA silencing: a novel stress-induced mechanism in Trypanosoma brucei

Yaniv Lustig; Lilach Sheiner; Yaron Vagima; Hanoch Goldshmidt; Anish Das; Vivian Bellofatto; Shulamit Michaeli

doi:10.1038/sj.embor.7400930

Spliced-leader RNA silencing: a novel stress-induced mechanism in Trypanosoma brucei

EMBO Rep. 2007 Apr;8(4):408-13. doi: 10.1038/sj.embor.7400930. Epub 2007 Mar 9.

Authors

Yaniv Lustig¹, Lilach Sheiner, Yaron Vagima, Hanoch Goldshmidt, Anish Das, Vivian Bellofatto, Shulamit Michaeli

Affiliation

¹ The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Hydrogen-Ion Concentration
Promoter Regions, Genetic
Protozoan Proteins / analysis
Protozoan Proteins / genetics
Protozoan Proteins / metabolism
RNA Interference
RNA, Messenger / metabolism
RNA, Spliced Leader / antagonists & inhibitors
RNA, Spliced Leader / genetics
RNA, Spliced Leader / physiology*
Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / physiology*
Receptors, Peptide / antagonists & inhibitors
Receptors, Peptide / genetics
Receptors, Peptide / physiology*
Ribosomes / metabolism
Transcription Factors / analysis
Transcription Factors / genetics
Transcription Factors / metabolism
Trypanosoma brucei brucei / chemistry
Trypanosoma brucei brucei / genetics
Trypanosoma brucei brucei / growth & development*

Substances

Protozoan Proteins
RNA, Messenger
RNA, Spliced Leader
Receptors, Cytoplasmic and Nuclear
Receptors, Peptide
Transcription Factors
signal peptide receptor