Abstract
Pervasive transcription of the genome produces a diverse array of functional non-coding RNAs (ncRNAs). One particular class of ncRNAs, long intervening non-coding RNAs (lincRNAs) are thought to play a role in regulating gene expression and may be a major contributor to organism and tissue complexity. The human brain with its heterogeneous cellular make-up is a rich source of lincRNAs; however, the functions of the majority of lincRNAs are unknown. Recently, by completing RNA sequencing (RNA-Seq) of the human frontal cortex, we identified linc00320 as being highly expressed in the white matter compared to grey matter in multiple system atrophy (MSA) brain. Here, we further investigate the expression patterns of linc00320 and conclude that it is involved in specific brain regions rather than having involvement in the MSA disease process. We also show that the full-length linc00320 is only expressed in human brain tissue and not in other primates, suggesting that it may be involved in improved functional connectivity for higher human brain cognition.
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Acknowledgments
Tissues were received from the Sydney Brain Bank at Neuroscience Research Australia and the New South Wales Tissue Resource Centre at the University of Sydney which are supported by the National Health and Medical Research Council of Australia (NHMRC), University of New South Wales, Neuroscience Research Australia, Schizophrenia Research Institute, and National Institute of Alcohol Abuse and Alcoholism (NIH (NIAAA) R24AA012725). This research was supported by the National Health & Medical Research Council of Australia (Project grant #1022325 to WSK and Fellowship #630434 to GMH) and Brain Foundation Australia (to MJ). EA is supported by the Framework Programme FP7/2007-2013 under the project EPISTOP (grant agreement n°: 602391) and (NeuroGeM grant 733051052).
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Supplementary Figure 1
Conservation and expression of linc00320 in mammals. For each species a brain RNA-seq read coverage track across the locus is shaded blue. Read depth scales are different between species. On the human track the linc00320 exons were numbered and highlighted in green. Expression of the last exon was only observed in human. Light blue shaded tracks (for species other than human) are BLASTN hits of each human linc00320 (ENST00000416768) exon to the respective genomes. Exons are colored differently, and the percentage of homology shared with the human linc00320 is listed after the exon names. (PDF 1585 kb)
Supplementary Figure 2
RNA secondary structure as predicted by RNAfold and region that interacts with the selected RNA-binding proteins. The color of the bases indicates how likely those bases are to pair, with red indicated maximum likely hood and blue indicating unlikely. The common 3’ exon of each isoforms results in a common secondary structure for all of the linc00320 isoforms. The area of RNA-binding protein interaction is highlighted in purple. Interestingly the RNA-binding protein interaction area comprises a similar structural motif in each isoform. The starting point of each exon is indicated with a black bar and indication of the exon number, as well as the 5’ and 3’ end of the folded transcript. A. linc00320-002 B. linc00320-006 C. linc00320-007. (GIF 5 kb)
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Supplementary Figure 3
Interaction profile of each linc00320 transcript and selected RNA-binding proteins. A. Linc00320-006 B. Linc00320-007. The x-axis indicates the nucleotide position along the transcript. The interaction score on the y-axis indicates how likely it is for the RNA-binding protein to interact with this region of the transcript. The peak of 3.5 between approximately 150–300 indicates that this is a likely area of interaction. Two experimentally validated predictions, the interaction between the Fmr1 protein and its mRNA and the interaction between Srsf1 and the long non-coding RNA Xist give interaction scores of close to 4 [30, 31]. The prediction is based on structural properties, further analysis also showed that sequence motifs are present for each of the RNA-binding proteins. (GIF 478 kb)
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Mills, J.D., Chen, J., Kim, W.S. et al. Long intervening non-coding RNA 00320 is human brain-specific and highly expressed in the cortical white matter. Neurogenetics 16, 201–213 (2015). https://doi.org/10.1007/s10048-015-0445-1
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DOI: https://doi.org/10.1007/s10048-015-0445-1