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Functional characterisation of long intergenic non-coding RNAs through genetic interaction profiling in Saccharomyces cerevisiae
- Source :
- BMC Biology, BMC Biol.
- Publication Year :
- 2016
-
Abstract
- Background 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). Results 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. Conclusions 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. Electronic supplementary material The online version of this article (doi:10.1186/s12915-016-0325-7) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Saccharomyces cerevisiae Proteins
Physiology
Saccharomyces cerevisiae
Genomics
Plant Science
Genome
General Biochemistry, Genetics and Molecular Biology
Long intergenic non-coding RNAs
Transcriptome
Synthetic genetic array
03 medical and health sciences
Structural Biology
DNA, Fungal
Gene
Telomerase
Ecology, Evolution, Behavior and Systematics
Genetics
biology
Agricultural and Biological Sciences(all)
Biochemistry, Genetics and Molecular Biology(all)
Gene Expression Profiling
Genetic interactions
Cell Biology
Telomere
biology.organism_classification
Gene expression profiling
030104 developmental biology
Exodeoxyribonucleases
Gene Ontology
RNA, Long Noncoding
Genome, Fungal
Stable unannotated transcripts
General Agricultural and Biological Sciences
Developmental Biology
Biotechnology
Research Article
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- BMC Biology, BMC Biol.
- Accession number :
- edsair.doi.dedup.....cda33498be3f3481dabd806381824638