title: Functional characterisation of long intergenic non-coding RNAs through genetic interaction profiling in Saccharomyces cerevisiae.
abstract: Transcriptome studies have revealed that many eukaryotic genomes are pervasively transcribed producing numerous long non-coding RNAs (lncRNAs). However, only a few lncRNAs have been ascribed a cellular role thus far, with most regulating the expression of adjacent genes. Even less lncRNAs have been annotated as essential hence implying that the majority may be functionally redundant. Therefore, the function of lncRNAs could be illuminated through systematic analysis of their synthetic genetic interactions (GIs).
  
  
  
  Here, we employ synthetic genetic array (SGA) in Saccharomyces cerevisiae to identify GIs between long intergenic non-coding RNAs (lincRNAs) and protein-coding genes. We first validate this approach by demonstrating that the telomerase RNA TLC1 displays a GI network that corresponds to its well-described function in telomere length maintenance. We subsequently performed SGA screens on a set of uncharacterised lincRNAs and uncover their connection to diverse cellular processes. One of these lincRNAs, SUT457, exhibits a GI profile associating it to telomere organisation and we consistently demonstrate that SUT457 is required for telomeric overhang homeostasis through an Exo1-dependent pathway. Furthermore, the GI profile of SUT457 is distinct from that of its neighbouring genes suggesting a function independent to its genomic location. Accordingly, we show that ectopic expression of this lincRNA suppresses telomeric overhang accumulation in sut457Δ cells assigning a trans-acting role for SUT457 in telomere biology.
  
  
  
  Overall, our work proposes that systematic application of this genetic approach could determine the functional significance of individual lncRNAs in yeast and other complex organisms.
authors.affiliation: Department of Biological Sciences, University of Cyprus, Nicosia, CY-1678, Cyprus.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kyriakou
authors.affiliation: Department of Biological Sciences, University of Cyprus, Nicosia, CY-1678, Cyprus.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Stavrou
authors.affiliation: Department of Biological Sciences, University of Cyprus, Nicosia, CY-1678, Cyprus.
authors.forename: Panayiota
authors.initials: P
authors.lastname: Demosthenous
authors.affiliation: Department of Biological Sciences, University of Cyprus, Nicosia, CY-1678, Cyprus.
authors.forename: Georgia
authors.initials: G
authors.lastname: Angelidou
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, M5S 3E1, Canada.
authors.forename: Bryan-Joseph
authors.initials: BJ
authors.lastname: San Luis
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, M5S 3E1, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
authors.affiliation: Department of Biological Sciences, University of Cyprus, Nicosia, CY-1678, Cyprus.
authors.forename: Vasilis J
authors.initials: VJ
authors.lastname: Promponas
authors.affiliation: Department of Biological Sciences, University of Cyprus, Nicosia, CY-1678, Cyprus. kirmizis@ucy.ac.cy.
authors.forename: Antonis
authors.identifier: 0000-0002-3748-8711
authors.initials: A
authors.lastname: Kirmizis
mesh_terms: D004271:DNA, Fungal / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D063990:Gene Ontology; D016681:Genome, Fungal; D023281:Genomics; D062085:RNA, Long Noncoding / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics*
chemical_list: D004271:DNA, Fungal; D062085:RNA, Long Noncoding; D029701:Saccharomyces cerevisiae Proteins; D019098:Telomerase; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I
keywords: Genetic interactions; Long intergenic non-coding RNAs; Stable unannotated transcripts; Synthetic genetic array; Telomere