Aufsatz
Artikel (Publikationen im Open Access gefördert durch die UB)
Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling
Abstract
Previous work in yeast has suggested that modification of tRNAs, in particular uridine bases in the anticodon wobble position (U34), is linked to TOR (target of rapamycin) signaling. Hence, U34 modification mutants were found to be hypersensitive to TOR inhibition by rapamycin. To study whether this involves inappropriate TOR signaling, we examined interaction between mutations in TOR pathway genes (tip41Δ, sap190Δ, ppm1Δ, rrd1Δ) and U34 modification defects (elp3Δ, kti12Δ, urm1Δ, ncs2Δ) and found the rapamycin hypersensitivity in the latter is epistatic to drug resistance of the former. Epistasis, however, is abolished in tandem with a gln3Δ deletion, which inactivates transcription factor Gln3 required for TOR-sensitive activation of NCR (nitrogen catabolite repression) genes. In line with nuclear import of Gln3 being under control of TOR and dephosphorylation by the Sit4 phosphatase, we identify novel TOR-sensitive sit4 mutations that confer rapamycin resistance and importantly, mislocalise Gln3 when TOR is inhibited. This is similar to gln3Δ cells, which abolish the rapamycin hypersensitivity of U34 modification mutants, and suggests TOR deregulation due to tRNA undermodification operates through Gln3. In line with this, loss of U34 modifications (elp3Δ, urm1Δ) enhances nuclear import of and NCR gene activation (MEP2, GAP1) by Gln3 when TOR activity is low. Strikingly, this stimulatory effect onto Gln3 is suppressed by overexpression of tRNAs that usually carry the U34 modifications. Collectively, our data suggest that proper TOR signaling requires intact tRNA modifications and that loss of U34 modifications impinges on the TORsensitive NCR branch via Gln3 misregulation.
Citation
In: Microbial cell. - Graz : Shared Science Publ., 2014, Vol. 1, 12, 416-424Sponsorship
Gefördert durch den Publikationsfonds der Universität KasselCollections
Publikationen (Fachgebiet Mikrobiologie)Artikel (Publikationen im Open Access gefördert durch die UB)
Citation
@article{urn:nbn:de:hebis:34-2015031347687,
author={Scheidt, Viktor and Jüdes, André and Bär, Christian and Klassen, Roland and Schaffrath, Raffael},
title={Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling},
year={2014}
}
0500 Oax 0501 Text $btxt$2rdacontent 0502 Computermedien $bc$2rdacarrier 1100 2014$n2014 1500 1/eng 2050 ##0##urn:nbn:de:hebis:34-2015031347687 3000 Scheidt, Viktor 3010 Jüdes, André 3010 Bär, Christian 3010 Klassen, Roland 3010 Schaffrath, Raffael 4000 Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling / Scheidt, Viktor 4030 4060 Online-Ressource 4085 ##0##=u http://nbn-resolving.de/urn:nbn:de:hebis:34-2015031347687=x R 4204 \$dAufsatz 4170 7136 ##0##urn:nbn:de:hebis:34-2015031347687
2015-03-13T11:42:22Z 2015-03-13T11:42:22Z 2014 2311-2638 urn:nbn:de:hebis:34-2015031347687 http://hdl.handle.net/123456789/2015031347687 Gefördert durch den Publikationsfonds der Universität Kassel eng Urheberrechtlich geschützt https://rightsstatements.org/page/InC/1.0/ 570 Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling Aufsatz Previous work in yeast has suggested that modification of tRNAs, in particular uridine bases in the anticodon wobble position (U34), is linked to TOR (target of rapamycin) signaling. Hence, U34 modification mutants were found to be hypersensitive to TOR inhibition by rapamycin. To study whether this involves inappropriate TOR signaling, we examined interaction between mutations in TOR pathway genes (tip41Δ, sap190Δ, ppm1Δ, rrd1Δ) and U34 modification defects (elp3Δ, kti12Δ, urm1Δ, ncs2Δ) and found the rapamycin hypersensitivity in the latter is epistatic to drug resistance of the former. Epistasis, however, is abolished in tandem with a gln3Δ deletion, which inactivates transcription factor Gln3 required for TOR-sensitive activation of NCR (nitrogen catabolite repression) genes. In line with nuclear import of Gln3 being under control of TOR and dephosphorylation by the Sit4 phosphatase, we identify novel TOR-sensitive sit4 mutations that confer rapamycin resistance and importantly, mislocalise Gln3 when TOR is inhibited. This is similar to gln3Δ cells, which abolish the rapamycin hypersensitivity of U34 modification mutants, and suggests TOR deregulation due to tRNA undermodification operates through Gln3. In line with this, loss of U34 modifications (elp3Δ, urm1Δ) enhances nuclear import of and NCR gene activation (MEP2, GAP1) by Gln3 when TOR activity is low. Strikingly, this stimulatory effect onto Gln3 is suppressed by overexpression of tRNAs that usually carry the U34 modifications. Collectively, our data suggest that proper TOR signaling requires intact tRNA modifications and that loss of U34 modifications impinges on the TORsensitive NCR branch via Gln3 misregulation. open access In: Microbial cell. - Graz : Shared Science Publ., 2014, Vol. 1, 12, 416-424 Scheidt, Viktor Jüdes, André Bär, Christian Klassen, Roland Schaffrath, Raffael doi:10.15698/mic2014.12.179
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