Research in my laboratory explores the regulation of gene expression by small RNAs. Our main focus is on microRNAs (miRNAs), which are ~20 nucleotide RNAs that repress gene expression by base-pairing to messenger RNAs transcribed from specific protein-coding genes. Recent work indicates that more than half of human protein-coding genes are regulatory targets of miRNAs. My lab will examine the roles that miRNAs play during growth and development, how miRNAs contribute to speciation, and how miRNA misregulation can lead to oncogenesis.
Goal 1 – Ascertain microRNA molecular origins to facilitate target prediction.
Computationally predicting miRNA targets. Active transposable elements (TEs) regularly integrate into inter- and intragenic regions. Since numerous miRNAs have now been identified as being formed from TEs, and miRNAs target mRNAs through complementarity, logic dictates that a miRNA regulates transcripts baring copies of its progenitor TE. In our lab, student researchers are trained to actively search characterized and novel genomes alike for functional miRNA targets. Students identify putative miRNA::target mRNA relationships through using a unique computational strategy which limits miRNA target searches to transcripts containing that miRNA’s progenitor TE.
Goal 2 - Identify novel genomic repeat and microRNA compositions
Another focus of our lab is de novo genome sequencing using the departmental Ion Torrent Next Gen sequencer as well as training students in the retrieval of sequences from publicly available datasets. Following sequence acquisition, students are trained how to annotate these using web-based applications, and how to use alignment software to identify genomic hairpins, putative miRNAs, and novel repeats.
Goal 3 – Characterize novel prokaryotic and eukaryotic small RNAs.
I wholly believe that life arose from small RNA interactions. I further believe that life and all cellular activity are still coordinated by small, noncoding RNA biology. Unfortunately due to their small size, the vast majority of small, noncoding RNAs remain undescribed. Another focus of my laboratory is the sequencing of small RNA populations from a variety of prokaryotic and eukaryotic species.
Goal 4 - Characterize miRNA misregulations with casual roles in oncogenesis.
Utilizing many of the tools described above, my students also computationally examine additional putative (potentially causal) microRNA interactions through exploring publicly available small RNA libraries derived from specific oncologies.
Daniel Warren , Bob Thomson , Les Buck, H. Bradley Shaffer , Andrew M Shedlock, Nicole Valenzuela , M Fujita, Chris Ponting, AB Roniko, Rachel Bowden , Blanche Capel , Alisha Holloway, Phillip Spinks, Ramkumar Hariharan , Kenneth Storey , Fred Janzen , Suzanne McGaugh, Glen Borchert , LaDeana Hillier, Pat Minx. Genome sequence and analysis of the painted tortoise genome. 2012. In preparation.
Edward A. Ehrat, Bradley R. Johnson, Jonathan D. Williams, Glen M Borchert, Erik D Larson. G-quadruplex recognition activities of E. coli MutS. BMC Molecular Biology. 2012, 13:23.
Teresa J. Filshtein and Craig O. Mackenzie, Maurice D. Dale, Paul S. Dela-Cruz, Dale M. Ernst, Edward A Frankenberger, Chunyan He, Kaylee L. Heath, Andria S. Jones, Daniel K. Jones, Edward R. King, Maggie B. Maher, Travis J. Mitchell, Rachel R. Morgan, Sirisha Sirobhushanam, Scott D. Halkyard, Kiran B. Tiwari, David Rubin, Erik D Larson, Glen M. Borchert. OrbID: MicroRNA Origin Based microRNA target identification. Mobile Genetic Elements. May/June 2012, 2:3, 1-9.
Glen M Borchert, Nathaniel W Holton, Erik D Larson. Repression of human Activation Induced cytidine Deaminase by miR-93 and miR-155. BMC Cancer. 2011 Aug 11:347.
Glen M. Borchert, Nathaniel W. Holton, Jonathan D. Williams, William L. Hernan, Ian P. Bishop, Joel A. Dembosky, James E. Elste, Nathaniel S. Gregoire, Jee-Ah Kim, Wesley W. Koehler, Joe C. Lengerich, Arianna A. Medema, Marilyn A. Nguyen, Geoffrey D. Ower, Michelle A. Rarick, Brooke N. Strong, Nicholas J. Tardi, Nathan M. Tasker, Darren J. Wozniak, Craig Gatto and Erik D. Larson. Comprehensive analysis of microRNA genomic loci identifies pervasive repetitive-element origins. Mobile Genetic Elements. 2011 May/June: 1(1): 8-17.
William Lanier, Heather M. Tyra, Eric J. Devor, Glen Borchert, Josep Comeron, Debashish Bhattacharya. From simple beginnings: the evolution of miRNAs from transposable elements in Chlamydomonas reinhardtii. 2011. PLoS Genetics. In revision.
GM Borchert, Holden NW, Vogel LA, Edwards KA, ED Larson. Histone H2A and H2B are monoubiquitinated at AID-targeted loci. PLoS One. 2010 Jul 16;5(7):e11641.
GM Borchert, Gilmore BL, Spengler RM, Xing Y, Lanier W, Bhattacharya D, Davidson BL. Adenosine deamination in human transcripts generates novel microRNA binding sites. Human Molecular Genetics. 2009 18(24):4801-4807.
GM Borchert, W Lanier and BL Davidson. RNA polymerase III transcribes human microRNAs. Nature Structural & Molecular Biology. 2006 Dec;13(12):1097-101.