Wang, Changliang, Knott, K. Emily, Heikkinen, Liisa, Yang, Yang, Chen, Liang, Wong, Garry
[
International Worm Meeting,
2019]
microRNAs (miRNAs) are a class of small noncoding RNA derived from primary miRNA transcripts and processed into precursors and eventually to mature miRNAs 21-22 nucleotides in length. miRNAs were originally discovered in C. elegans and are now known to be expressed in animals, plants, and viruses. miRNAs exert their actions as important regulators of cell proliferation, growth, and development via RNA silencing mechanisms. Bioinformatics resources for miRNA study have been developed, but identifying a correct tool for a specific application is tedious and laborious. In order to facilitate this process, we developed a database portal named miRToolsGallery by manual curation of approximately 1000 tools and resources. With miRToolsGallery, a user can easily locate the appropriate tool for an investigation by implementing a searchable and rankable query function. Tools are ranked by different criteria from PageRank algorithm to most recent publication date to number of publications. The portal contains tools covering a broad range of organisms including C. elegans. The tools also encompass an expansive range of applications from target identification to orthology search. Moreover, the tool is a rapid way to locate recent literature within the miRNA bioinformatics field and to identify current trends. One such trend identified with the tool was the stability and frequent use of some very old computational tools, despite the rapid and enormous advancement in knowledge of miRNA function. The resource is available at www.mirtoolsgallery.org. This research was supported in part by the Research grant of Garry Wong MYRG2016-00101-FHS.
[
J Biol Chem,
2002]
Collagen glucosyltransferase (GGT) activity has recently been shown to be associated with human lysyl hydroxylase (LH) isoform 3 (LH3) (Heikkinen, J., Risteli, M., Wang, C., Latvala, J., Rossi, M., Valtavaara, M., Myllyla, R. (2000) J. Biol. Chem. 275, 36158-36163). The LH and GGT activities of the multifunctional LH3 protein modify lysyl residues in collagens posttranslationally to form hydroxylysyl and glucosylgalactosyl hydroxylysyl residues respectively. We now report that in the nematode, Caenorhabditis elegans, where only one ortholog is found for lysyl hydroxylase, the LH and GGT activities are also associated with the same gene product. The aim of the present studies is the identification of amino acids important for the catalytic activity of GGT. Our data indicate that the GGT active site is separate from the carboxyl-terminal LH active site of human LH3, the amino acids important for the GGT activity being located at the amino-terminal part of the molecule. Site-directed mutagenesis of a conserved cysteine at position 144 to isoleucine and a leucine at position 208 to isoleucine caused a marked reduction in GGT activity. These amino acids were conserved in C. elegans LH and mammalian LH3, but not in LH1 or LH2, which lack GGT activity. The data also reveal a DXD-like motif in LH3 characteristic of many glycosyltransferases and the mutagenesis of aspartates of this motif eliminated the GGT activity. Reduction in GGT activity was not accompanied by a change in the LH activity of the molecule. Thus GGT activity can be manipulated independently of LH activity in LH3. These data provide the information needed to design knock-out studies for investigation of the function of glucosylgalactosyl hydroxylysyl residues of collagens in vivo.