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

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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 (SRα) 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.

Original languageEnglish (US)
Pages (from-to)408-413
Number of pages6
JournalEMBO Reports
Volume8
Issue number4
DOIs
StatePublished - Apr 2007

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics

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