title: Global identification of conserved post-transcriptional regulatory programs in trypanosomatids.
abstract: While regulatory programs are extensively studied at the level of transcription, elements that are involved in regulation of post-transcriptional processes are largely unknown, and methods for systematic identification of these elements are in early stages. Here, using a novel computational framework, we have integrated sequence information with several functional genomics data sets to characterize conserved regulatory programs of trypanosomatids, a group of eukaryotes that almost entirely rely on post-transcriptional processes for regulation of mRNA abundance. This analysis revealed a complex network of linear and structural RNA elements that potentially govern mRNA abundance across different life stages and environmental conditions. Furthermore, we show that the conserved regulatory network that we have identified is responsive to chemical perturbation of several biological functions in trypanosomatids. We have further characterized one of the most abundant regulatory RNA elements that we discovered, an AU-rich element (ARE) that can be found in 3' untranslated region of many trypanosomatid genes. Using bioinformatics approaches as well as in vitro and in vivo experiments, we have identified three ELAV-like homologs, including the developmentally critical protein TbRBP6, which regulate abundance of a large number of trypanosomatid ARE-containing transcripts. Together, these studies lay out a roadmap for characterization of mechanisms that modulate development and metabolic pathways in trypanosomatids.
authors.affiliation: Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste. Anne de Bellevue, Montreal, Quebec H9X 3V9, Canada, McGill Centre for Bioinformatics, McGill University, 3649 Promenade Sir William Osler, Montreal, Quebec H3G 0B1, Canada, Department of Human Genetics, McGill University Health Centre, Montréal, Québec, Canada, McGill University and Genome Québec Innovation Centre, Montréal, Québec H3A 1A4, Canada, Department of Medical Genetics, McGill University Health Centre, Montréal, Québec, Canada and Department of Biochemistry, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada.
authors.forename: Hamed S
authors.initials: HS
authors.lastname: Najafabadi
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Lu
authors.forename: Chad
authors.initials: C
authors.lastname: MacPherson
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Mehta
authors.forename: Véronique
authors.initials: V
authors.lastname: Adoue
authors.forename: Tomi
authors.initials: T
authors.lastname: Pastinen
authors.forename: Reza
authors.initials: R
authors.lastname: Salavati
mesh_terms: D020413:3' Untranslated Regions; D051959:ELAV Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D059372:Nucleotide Motifs; D015800:Protozoan Proteins / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016053:RNA, Protozoan / Q000737:chemistry* / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D018085:Regulon; D014345:Trypanosoma / Q000235:genetics; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D051959:ELAV Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger; D016053:RNA, Protozoan; D038621:Regulatory Sequences, Ribonucleic Acid