Genome-wide identification of tissue-specific long non-coding RNA in three farm animal species

Authors: KERN, COLIN - University Of California, Davis; WANG, YING - University Of California, Davis; CHITWOOD, JAMES - University Of California, Davis; KORF, IAN - University Of California, Davis; DELANY, MARY - University Of California, Davis; Cheng, Hans; MEDRANO, JUAN - University Of California, Davis; VAN EENENNAAM, ALISON - University Of California, Davis; ERNST, CATHERINE - Michigan State University; ROSS, PABLO - University Of California, Davis; ZHOU, HUAIJUN - University Of California, Davis

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/26/2018
Publication Date: 9/18/2018
Citation: Kern, C., Wang, Y., Chitwood, J., Korf, I., DeLany, M., Cheng, H.H., Medrano, J.F., Van Eenennaam, A.L., Ernst, C., Ross, P., Zhou, H. 2018. Genome-wide identification of tissue-specific long non-coding RNA in three farm animal species. BMC Genomics. 19:684. https://doi.org/10.1186/s12864-018-5037-7.
DOI: https://doi.org/10.1186/s12864-018-5037-7

Interpretive Summary: With the advent of full genome sequences for many organisms, biology is rapidly focusing on and utilizing genomics. While genome assemblies and the identification of coding genes greatly enhanced our ability to connect DNA sequence (genotype) to traits of interest (phenotype), it becoming clear that genomes need to be more comprehensively annotated, especially with respect to regulatory elements. In this submission, the chicken, cattle, and pig genomes were surveyed for what is known as long non-coding RNAs, which help to regulate gene expression. The resulting information helps define how genes can be regulated and should enable better predictive biology for farm animals.

Technical Abstract: Background Numerous long non-coding RNAs (lncRNAs) have been identified and their roles on gene regulation in humans, mice, and other model organisms have been studied; however, far less research has been focused on lncRNAs in other animals, especially farm animals. While previous studies in chickens, cattle, and pigs have identified lncRNAs in developmental stages or differentially expressed under specific conditions in a limited number of tissues, more comprehensive identification of lncRNAs in these species is needed. The goal of the FAANG Consortium (Functional Annotation of Animal Genomes) is to functionally annotate animal genomes, which includes the annotation of lncRNAs. As one of the FAANG pilot projects, lncRNAs were identified across eight tissues in two adult male biological replicates from chickens, cattle, and pigs. Results Comprehensive lncRNA annotations for the chicken, cattle, and pig genomes were generated by utilizing RNA-seq from unique tissue samples with the same eight tissues at the same development stage (mature) and two biological replicates in each species. A total of 9,393 lncRNA transcripts from 4,654 loci in chickens, 7,235 lncRNA from 4,325 loci in cattle, and 14,428 lncRNA from 8,772 loci in pigs were identified, with about half consisting of previously unannotated lncRNAs. Including both novel isoforms and lncRNAs from novel loci, 5,288 novel lncRNAs were identified in chickens, 3,732 in cattle, and 4,870 in pigs. These transcripts match previously known patterns of lncRNA, such as generally lower expression levels than protein-coding genes and higher tissue specificity. An analysis of lncRNA conservation across species identified a set of conserved lncRNA with potential functions associated with chromatin structure and gene regulation. Tissue-specific lncRNA were identified, and genes nearby tissue-specific lncRNAs were enriched for GO terms associated with those tissues. For example, lncRNAs specific to spleen were nearby genes enriched in immune system related GO terms such as leukocyte activation. Conclusions LncRNAs have been identified in three important farm animal species using eight tissues from adult individuals. About half of the identified lncRNA were not previously annotated in the NCBI annotations for these species. While lncRNA are less conserved that protein-coding genes, a set of positionally conserved lncRNAs were found between chicken, cattle, and pig with potential functions related to chromatin structure and gene regulation. Tissue-specific lncRNA have potential regulatory functions on genes enriched for tissue-specific GO terms. Future work to include epigenetic data from ChIP-seq experiments will allow further refinement of these annotations.