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5-Methyluridine (m5U) is one of the most abundant RNA modifications found in cytosolic tRNA. tRNA methyltransferase 2 homolog A (hTRMT2A) is the dedicated mammalian enzyme for m5U formation at tRNA position 54. However, its RNA binding specificity and functional role in the cell are not well understood. Here we dissected structural and sequence requirements for binding and methylation of its RNA targets. Specificity of tRNA modification by hTRMT2A is achieved by a combination of modest binding preference and presence of a uridine in position 54 of tRNAs. Mutational analysis together with cross-linking experiments identified a large hTRMT2A–tRNA binding surface. Furthermore, complementing hTRMT2A interactome studies revealed that hTRMT2A interacts with proteins involved in RNA biogenesis. Finally, we addressed the question of the importance of hTRMT2A function by showing that its knockdown reduces translation fidelity. These findings extend the role of hTRMT2A beyond tRNA modification towards a role in translation.

© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P =.02). These findings may help to improve the management of SOT recipients. ispartof: American Journal of Transplantation vol:18 issue:7 pages:1745-1754 ispartof: location:United States status: published

Contains fulltext : 137617.pdf (Publisher’s version ) (Closed access) Patients with acute myeloid leukemia (AML) frequently harbor mutations in genes involved in the DNA (hydroxy)methylation pathway (DNMT3A, TET2, IDH1, and IDH2). In this study, we measured 5-hydroxymethylcytosine (5hmC) levels in 206 clinically and molecularly well-characterized younger adult AML patients (

SummaryTet proteins oxidize 5-methylcytosine (mC) to generate 5-hydroxymethyl (hmC), 5-formyl (fC), and 5-carboxylcytosine (caC). The exact function of these oxidative cytosine bases remains elusive. We applied quantitative mass-spectrometry-based proteomics to identify readers for mC and hmC in mouse embryonic stem cells (mESC), neuronal progenitor cells (NPC), and adult mouse brain tissue. Readers for these modifications are only partially overlapping, and some readers, such as Rfx proteins, display strong specificity. Interactions are dynamic during differentiation, as for example evidenced by the mESC-specific binding of Klf4 to mC and the NPC-specific binding of Uhrf2 to hmC, suggesting specific biological roles for mC and hmC. Oxidized derivatives of mC recruit distinct transcription regulators as well as a large number of DNA repair proteins in mouse ES cells, implicating the DNA damage response as a major player in active DNA demethylation.

The study of epigenetic changes that affect gene expression patterns seems of increasing importance during stem cell differentiation, ageing and tumorigenesis. Only 3 years ago a new modification has been found: 5-Hydroxymethylcytosine (5hmC). For a long time 5-methylcytosine (5mC) seemed to be the [for full text, please go to the a.m. URL], 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Numerous studies of the long-distance hole-migration process through a DNA double strand have revealed detailed insight into the distance and sequence dependence of charge-movement processes.[1-4] In contrast to the wealth of information nowavailable on the long-distance hole transfer,[5-9] less is known about the complementary excess-electron-transfer process in which an anion, instead of a cation, moves through the duplex.We,[10-13] and others,[14-19] have recently shown that excess electrons move through DNA by a hopping-type mechanism in which the pyrimidine bases dT and dC act as ,stepping stones

Model compounds for the study of the primary processes in photosynthesis continue to spur chemists on to elaborate syntheses. Latest efforts have resulted in the triple-decker compounds (“triads”) 1 and 2, in which two quinone and one porphyrin, and one quinone and two porphyrin units, respectively, are linked in rigid