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

Y Lustig; L Sheiner; Y Vagima; H Goldshmidt; A Das; V Bellofatto; S Michaeli

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

Y Lustig, L Sheiner, Y Vagima, H Goldshmidt, A Das, V Bellofatto, S Michaeli

The Mina and Everard Goodman Faculty of Life Sciences

Research output: Contribution to journal › Article › peer-review

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 language	American English
Pages (from-to)	407-413
Journal	EMBO Reports
Volume	8
Issue number	4
State	Published - 2007

Cite this

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title = "Spliced‐leader RNA silencing: a novel stress‐induced mechanism in Trypanosoma brucei",

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.",

author = "Y Lustig and L Sheiner and Y Vagima and H Goldshmidt and A Das and V Bellofatto and S Michaeli",

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T1 - Spliced‐leader RNA silencing: a novel stress‐induced mechanism in Trypanosoma brucei

AU - Lustig, Y

AU - Sheiner, L

AU - Vagima, Y

AU - Goldshmidt, H

AU - Das, A

AU - Bellofatto, V

AU - Michaeli, S

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

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M3 - Article

SN - 1469-221X

VL - 8

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JO - EMBO Reports

JF - EMBO Reports

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

Abstract

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