mRNA modifications: Dynamic regulators of gene expression?

Hoernes, Thomas Philipp; Hüttenhofer, Alexander; Erlacher, Matthias David

doi:10.1080/15476286.2016.1203504

Cited by 49 publications

(38 citation statements)

References 86 publications

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“…However, it cannot be excluded that the oxidative‐stress‐promoted desulfuration of thiolated wobble uridines represents an example of the stress‐regulated reading of synonymous codons in messenger RNA, which is further reflected in eventual protein biosynthesis. This phenomenon is widely discussed, especially in light of the recently identified modified nucleosides present in messenger RNA, which play a dominant role in the stress‐regulated dynamics of the translation process …”

Section: Discussionmentioning

confidence: 99%

Cytochrome cCatalyzes the Hydrogen Peroxide‐Assisted Oxidative Desulfuration of 2‐Thiouridines in Transfer RNAs

et al. 2018

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The 5-substituted 2-thiouridines (R5S2Us) present in the first (wobble) position of the anticodon of transfer RNAs (tRNAs) contribute to accuracy in reading mRNA codons and tuning protein synthesis. Previously, we showed that, under oxidative stress conditions in vitro, R5S2Us were sensitive to hydrogen peroxide (H O ) and that their oxidative desulfuration produced 5-substituted uridines (R5Us) and 4-pyrimidinone nucleosides (R5H2Us) at a ratio that depended on the pH and an R5 substituent. Here, we demonstrate that the desulfuration of 2-thiouridines, either alone or within an RNA/tRNA chain, is catalyzed by cytochrome c (cyt c). Its kinetics are similar to those of Fenton-type catalytic 2-thiouridine (S2U) desulfuration. Cyt c/H O - and Fe -mediated reactions deliver predominantly 4-pyrimidinone nucleoside (H2U)-type products. The pathway of the cyt c/H O -peroxidase-mediated S2U→H2U transformation through uridine sulfenic (U-SOH), sulfinic (U-SO H), and sulfonic (U-SO H) intermediates is confirmed by LC-MS. The cyt c/H O -mediated oxidative damage of S2U-tRNA may have biological relevance through alteration of the cellular functions of transfer RNA.

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Section: Discussionmentioning

confidence: 99%

Cytochrome cCatalyzes the Hydrogen Peroxide‐Assisted Oxidative Desulfuration of 2‐Thiouridines in Transfer RNAs

et al. 2018

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“…In addition to tRNA, the m 1 A modification was also identified on messenger RNA (mRNA) (reviewed in [51]). The modification was predominantly found in structured regions of the 5′ untranslated region, or close to canonical or alternative start codons [52,53], suggesting that also in mRNA this modification plays a role in RNA structural stability.…”

Section: The Biological Role Of M1a Modifications In Trnamentioning

confidence: 99%

m1A Post‐Transcriptional Modification in tRNAs

et al. 2017

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To date, about 90 post-transcriptional modifications have been reported in tRNA expanding their chemical and functional diversity. Methylation is the most frequent post-transcriptional tRNA modification that can occur on almost all nitrogen sites of the nucleobases, on the C5 atom of pyrimidines, on the C2 and C8 atoms of adenosine and, additionally, on the oxygen of the ribose 2′-OH. The methylation on the N1 atom of adenosine to form 1-methyladenosine (m1A) has been identified at nucleotide position 9, 14, 22, 57, and 58 in different tRNAs. In some cases, these modifications have been shown to increase tRNA structural stability and induce correct tRNA folding. This review provides an overview of the currently known m1A modifications, the different m1A modification sites, the biological role of each modification, and the enzyme responsible for each methylation in different species. The review further describes, in detail, two enzyme families responsible for formation of m1A at nucleotide position 9 and 58 in tRNA with a focus on the tRNA binding, m1A mechanism, protein domain organisation and overall structures.

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“…12 Recent studies suggest that RNA modifications allow for dynamic regulation of gene expression, and explain how rapid changes in protein synthesis can occur without requiring a change in overall levels of mRNA within cells. 31,32 …”

Section: Discussionmentioning

confidence: 99%

Prolongation of Relaxation Time in Extraocular Muscles With Brain Derived Neurotrophic Factor in Adult Rabbit

Nelson

Stevens

McLoon

2016

Invest. Ophthalmol. Vis. Sci.

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PurposeWe tested the hypothesis that short-term treatment with brain derived neurotrophic factor (BDNF) would alter the contractile characteristics of rabbit extraocular muscle (EOM).MethodsOne week after injections of BDNF in adult rabbit superior rectus muscles, twitch properties were determined in treated and control muscles in vitro. Muscles were also examined for changes in mean cross-sectional areas, neuromuscular junction size, and percent of myofibers expressing specific myosin heavy chain isoforms, and sarcoendoplasmic reticulum calcium ATPases (SERCA) 1 and 2.ResultsBrain derived neurotrophic factor–treated muscles had prolonged relaxation times compared with control muscles. Time to 50% relaxation, time to 100% relaxation, and maximum rate of relaxation were increased by 24%, 27%, and 25%, respectively. No significant differences were seen in time to peak force, twitch force, or maximum rate of contraction. Brain derived neurotrophic factor treatment significantly increased mean cross-sectional areas of slow twitch and tonic myofibers, with increased areas ranging from 54% to 146%. Brain derived neurotrophic factor also resulted in an increased percentage of slow twitch myofibers in the orbital layers, ranging from 54% to 77%, and slow-tonic myofibers, ranging from 44% to 62%. No significant changes were seen SERCA1 or 2 expression or in neuromuscular junction size.ConclusionsShort-term treatment with BDNF significantly prolonged the duration and rate of relaxation time and increased expression of both slow-twitch and slow-tonic myosin-expressing myofibers without changes in neuromuscular junctions or SERCA expression. The changes induced by BDNF treatment might have potential therapeutic value in dampening/reducing uncontrolled eye oscillations in nystagmus.

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mRNA modifications: Dynamic regulators of gene expression?

Cited by 49 publications

References 86 publications

Cytochrome cCatalyzes the Hydrogen Peroxide‐Assisted Oxidative Desulfuration of 2‐Thiouridines in Transfer RNAs

Cytochrome cCatalyzes the Hydrogen Peroxide‐Assisted Oxidative Desulfuration of 2‐Thiouridines in Transfer RNAs

m1A Post‐Transcriptional Modification in tRNAs

Prolongation of Relaxation Time in Extraocular Muscles With Brain Derived Neurotrophic Factor in Adult Rabbit

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