Human METTL18 is a histidine-specific methyltransferase that targets RPL3 and affects ribosome biogenesis and function

Protein methylation occurs primarily on lysine and arginine, but also on some other residues, such as histidine. METTL18 is the last uncharacterized member of a group of human methyltransferases (MTases) that mainly exert lysine methylation, and here we set out to elucidate its function. We found METTL18 to be a nuclear protein that contains a functional nuclear localization signal and accumulates in nucleoli. Recombinant METTL18 methylated a single protein in nuclear extracts and in isolated ribosomes from METTL18 knockout (KO) cells, identified as 60S ribosomal protein L3 (RPL3). We also performed an RPL3 interactomics screen and identified METTL18 as the most significantly enriched MTase. We found that His-245 in RPL3 carries a 3-methylhistidine (3MH; τ-methylhistidine) modification, which was absent in METTL18 KO cells. In addition, both recombinant and endogenous METTL18 were found to be automethylated at His-154, thus further corroborating METTL18 as a histidine-specific MTase. Finally, METTL18 KO cells displayed altered pre-rRNA processing, decreased polysome formation and codon-specific changes in mRNA translation, indicating that METTL18-mediated methylation of RPL3 is important for optimal ribosome biogenesis and function. In conclusion, we have here established METTL18 as the second human histidine-specific protein MTase, and demonstrated its functional relevance.     

Improving the performance of the EPT Index to accommodate multiple stressors in Afrotropical streams

The EPT index (Ephemeroptera, Plecoptera and Trichoptera) may be skewed by the wide tolerance to multiple stressors of the Baetid, Caenid and Hydropsychid families, which affects the performance of the EPT index as an indicator of multiple stressors in aquatic ecosystems. The effect of the BCH families on the EPT index was evaluated and alternatives were considered to improve its performance. The hypothesis that the removal of the BCH families improves sensitivity of the EPT index to human-induced stressors in streams and rivers was tested. Macroinvertebrates were collected in January–March 2009 at 22 sites in the Nyando and Nzoia Rivers, Lake Victoria basin, Kenya. Nine derivatives and modifications of the EPT index were tested for responses to a disturbance gradient, ranked into three condition categories (reference, intermediate and impaired). The sensitivity of the proportionate abundance derivative of the EPT index improved when the BCH families were removed, whereas that of the richness derivative improved marginally. Other modifications considered performed poorly when compared with the EPT-BCH metrics. Wide distribution of the BCH across all sites, irrespective of the level of disturbance, reduced the sensitivity of the EPT index in the studied streams. The removal of the BCH families enhanced the sensitivity of the index to multiple stressors in Afrotropical streams and rivers.