An evolutionary approach uncovers a diverse response of tRNA 2-thiolation to elevated temperatures in yeast

Alings, Fiona; Sarin, L. Peter; Fufezan, Christian; Drexler, Hannes C.A.; Leidel, Sebastian A.

doi:10.1261/rna.048199.114

Cited by 69 publications

(78 citation statements)

References 43 publications

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“…The condition employed in this study-a nonfermentable carbon source together with an elevated temperature-is known to lower tRNA transcription (Ciesla et al 2007). Also, the general level of tRNA modification was reported to change upon oxidative stress, DNA damage or hydroxyl peroxide and temperature (Chan et al 2010(Chan et al , 2012Alings et al 2015). Furthermore, hypomodified tRNAs or tRNAs containing mutations that destabilize their structure were shown to be degraded at elevated temperatures via the RTD pathway (Chernyakov et al 2008;Whipple et al 2011).…”

Section: Discussionmentioning

confidence: 83%

“…It has recently become appreciated that tRNA modifications that could alter the tRNA structure are affected by growth conditions. The effect of stress was reported for tRNA thiolation (Kamenski et al 2007;Damon et al 2015;Han et al 2015), m 5 C methylation (Preston et al 2013), and other modifications (Alings et al 2015). It is worth noting that activities of at least two enzymes responsible for end processing, RNase P and RNase Z, depend not on substrate sequence but proper structure (Takaku et al 2004;Mondragón 2013).…”

Section: Discussionmentioning

confidence: 92%

“…It has recently become appreciated that tRNA modifications are affected by stress (Chan et al 2010(Chan et al , 2012Preston et al 2013;Alings et al 2015;Damon et al 2015;Han et al 2015), but there are no reports regarding whether there is regulation of the activities responsible of pre-tRNA end-maturation. Here we investigated early steps of tRNA maturation for yeast grown at different temperatures (23°C-39°C) and in media with different carbon sources (glucose and glycerol).…”

Section: Introductionmentioning

confidence: 99%

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Control of Saccharomyces cerevisiae pre-tRNA processing by environmental conditions

Foretek

Hopper

et al. 2016

RNA

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tRNA is essential for translation and decoding of the proteome. The yeast proteome responds to stress and tRNA biosynthesis contributes in this response by repression of tRNA transcription and alterations of tRNA modification. Here we report that the stress response also involves processing of pre-tRNA 3 ′ termini. By a combination of Northern analyses and RNA sequencing, we show that upon shift to elevated temperatures and/or to glycerol-containing medium, aberrant pre-tRNAs accumulate in yeast cells. For pre-tRNA UAU Ile and pre-tRNA UUU Lys these aberrant forms are unprocessed at the 5 ′ ends, but they possess extended 3 ′ termini. Sequencing analyses showed that partial 3 ′ processing precedes 5 ′ processing for pre-tRNA UAU Ile . An aberrant pre-tRNA Tyr that accumulates also possesses extended 3 ′ termini, but it is processed at the 5 ′ terminus. Similar forms of these aberrant pretRNAs are detected in the rex1Δ strain that is defective in 3 ′ exonucleolytic trimming of pre-tRNAs but are absent in the lhp1Δ mutant lacking 3 ′ end protection. We further show direct correlation between the inhibition of 3 ′ end processing rate and the stringency of growth conditions. Moreover, under stress conditions Rex1 nuclease seems to be limiting for 3 ′ end processing, by decreased availability linked to increased protection by Lhp1. Thus, our data document complex 3 ′ processing that is inhibited by stress in a tRNA-type and condition-specific manner. This stress-responsive tRNA 3 ′ end maturation process presumably contributes to fine-tune the levels of functional tRNA in budding yeast in response to environmental conditions.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Control of Saccharomyces cerevisiae pre-tRNA processing by environmental conditions

Foretek

Hopper

et al. 2016

RNA

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“…However, in the last few years, it has become evident that the epitranscriptomic layer is not only dynamic and reversible (Jia et al 2011;Zheng et al 2013;Wang and He 2014;Liu et al 2016)-catalyzed by RNA modification "erasers" (Meyer and Jaffrey 2017)-but also that the activity of RNA modifications can be regulated by a wide variety of factors, including environmental conditions (Chan et al 2010;Dedon and Begley 2014;Alings et al 2015;Han et al 2015).…”

Section: Introductionmentioning

confidence: 99%

The RNA modification landscape in human disease

Jonkhout

Tran

Smith

et al. 2017

RNA

490

420

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RNA modifications have been historically considered as fine-tuning chemo-structural features of infrastructural RNAs, such as rRNAs, tRNAs, and snoRNAs. This view has changed dramatically in recent years, to a large extent as a result of systematic efforts to map and quantify various RNA modifications in a transcriptome-wide manner, revealing that RNA modifications are reversible, dynamically regulated, far more widespread than originally thought, and involved in major biological processes, including cell differentiation, sex determination, and stress responses. Here we summarize the state of knowledge and provide a catalog of RNA modifications and their links to neurological disorders, cancers, and other diseases. With the advent of direct RNA-sequencing technologies, we expect that this catalog will help prioritize those RNA modifications for transcriptome-wide maps.

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“…[43][44][45] Upon return to normal conditions, the modification level is restored. Under stress, the newly transcribed tRNA is not modified and the mature tRNA already available becomes unmodified, but seems not to be degraded to a significant extent.…”

Section: Glu(uuc)mentioning

confidence: 99%

tRNA wobble modifications and protein homeostasis

Ranjan

Rodnina

2016

Translation

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ABSTRACTtRNA is a central component of the protein synthesis machinery in the cell. In living cells, tRNAs undergo numerous post-transcriptional modifications. In particular, modifications at the anticodon loop play an important role in ensuring efficient protein synthesis, maintaining protein homeostasis, and helping cell adaptation and survival. Hypo-modification of the wobble position of the tRNA anticodon loop is of particular relevance for translation regulation and is implicated in various human diseases. In this review we summarize recent evidence of how methyl and thiol modifications in eukaryotic tRNA at position 34 affect cellular fitness and modulate regulatory circuits at normal conditions and under stress.

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An evolutionary approach uncovers a diverse response of tRNA 2-thiolation to elevated temperatures in yeast

Cited by 69 publications

References 43 publications

Control of Saccharomyces cerevisiae pre-tRNA processing by environmental conditions

Control of Saccharomyces cerevisiae pre-tRNA processing by environmental conditions

The RNA modification landscape in human disease

tRNA wobble modifications and protein homeostasis

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