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Non-coding RNAs match the deleted genomic regions in humans.

ABSTRACT: RNA is transcribed from DNA, and therefore, there should be no RNA transcript from the deleted DNA region. Our study attempted to analyse whether any RNA cache that maps the deleted regions is present in human cells. Using data from the 1000 genome project, we selected 41 CEPH (CEU) and 38 Yoruba (YRI) samples that included the data for the entire genome sequence and ncRNA and mRNA sequences. Aligning the ncRNA reads against the genomic DNA in individual samples has revealed that 229 out of 1114 homozygous deletions have ncRNA reads that map to them. Further analysis has revealed that ncRNA reads that map the deleted regions are enriched around the deletion ends and at genic regions of the genome. The read enrichment at deletion ends suggests that these ncRNAs are likely some form of double-strand break induced RNAs. Our analysis suggests that human cells may contain a residual ncRNA cache that is possibly propagated across generations.

SUBMITTER: Byeon B

PROVIDER: S-EPMC5112596 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Non-coding RNAs match the deleted genomic regions in humans.

Byeon Boseon B Kovalchuk Igor I

Scientific reports 20161117

RNA is transcribed from DNA, and therefore, there should be no RNA transcript from the deleted DNA region. Our study attempted to analyse whether any RNA cache that maps the deleted regions is present in human cells. Using data from the 1000 genome project, we selected 41 CEPH (CEU) and 38 Yoruba (YRI) samples that included the data for the entire genome sequence and ncRNA and mRNA sequences. Aligning the ncRNA reads against the genomic DNA in individual samples has revealed that 229 out of 1114 ...[more]

PMID: 27853310

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Project description:BackgroundAutism spectrum disorders (ASD) manifest with neurodevelopmental phenotypes including communicative, social and behavioral impairments that affect as many as 1 in 88 children. The majority of autism cases have no known genetic cause, suggesting complex genetics of the disorder, but a few genes of large effect have been identified.MethodsIn order to identify novel ASD genetic correlates, we investigated non-protein coding RNAs (ncRNAs) which are abundantly transcribed from the human genome, enriched in the brain, and have been implicated in neurodevelopmental disorders. Using an algorithm that we developed, we examined a publicly available transcriptomics database, AceView, to identify the natural antisense transcripts (NATs) that overlap with known autism-related genes. We validated the presence and differential expression of NATs in different brain regions of ASD and control brains using qRT-PCR. Additionally, we investigated the subcellular localization of these transcripts in a neuronal cell line using RNA-sequencing (RNA-seq).ResultsWe found noncoding antisense RNA transcripts at approximately 40% of loci previously implicated in ASD. We confirmed the expression of 10 antisense RNAs in different postmortem human brain tissues. The expression of five antisense transcripts was found to be region-specific, suggesting a role for these ncRNAs in the development and function of specific brain regions. Some antisense RNAs overlapping suspected ASD genes exhibited concordant expression relative to their sense protein-coding genes, while other sense-antisense pairs demonstrate a discordant relationship. Interestingly, the antisense RNA corresponding to the SYNGAP1 locus (SYNGAP1-AS) was found to be differentially expressed in brain regions of patients with ASD compared to control individuals. RNA-seq analysis of subcellular compartments from SH-SY5Y human neuroblastoma cells demonstrated that antisense RNAs to ASD candidate genes are predominantly expressed in the nucleoplasmic or chromatin compartments, implying their involvement in nuclear-associated processes.ConclusionsOur data suggests that NATs are abundantly expressed from ASD-related loci and provide evidence for their roles in target gene regulation, neurodevelopment and autism pathogenesis. This class of RNA should therefore be considered in functional studies aimed at understanding genetic risk factors for ASD.

Project description:We used RNA sequencing to analyze transcript profiles of ten autopsy brain regions from ten subjects. RNA sequencing techniques were designed to detect both coding and non-coding RNA, splice isoform composition, and allelic expression. Brain regions were selected from five subjects with a documented history of smoking and five non-smokers. Paired-end RNA sequencing was performed on SOLiD instruments to a depth of >40 million reads, using linearly amplified, ribosomally depleted RNA. Sequencing libraries were prepared with both poly-dT and random hexamer primers to detect all RNA classes, including long non-coding (lncRNA), intronic and intergenic transcripts, and transcripts lacking poly-A tails, providing additional data not previously available. The study was designed to generate a database of the complete transcriptomes in brain region for gene network analyses and discovery of regulatory variants.Of 20,318 protein coding and 18,080 lncRNA genes annotated from GENCODE and lncipedia, 12 thousand protein coding and 2 thousand lncRNA transcripts were detectable at a conservative threshold. Of the aligned reads, 52 % were exonic, 34 % intronic and 14 % intergenic. A majority of protein coding genes (65 %) was expressed in all regions, whereas ncRNAs displayed a more restricted distribution. Profiles of RNA isoforms varied across brain regions and subjects at multiple gene loci, with neurexin 3 (NRXN3) a prominent example. Allelic RNA ratios deviating from unity were identified in?>?400 genes, detectable in both protein-coding and non-coding genes, indicating the presence of cis-acting regulatory variants. Mathematical modeling was used to identify RNAs stably expressed in all brain regions (serving as potential markers for normalizing expression levels), linked to basic cellular functions. An initial analysis of differential expression analysis between smokers and nonsmokers implicated a number of genes, several previously associated with nicotine exposure.RNA sequencing identifies distinct and consistent differences in gene expression between brain regions, with non-coding RNA displaying greater diversity between brain regions than mRNAs. Numerous RNAs exhibit robust allele selective expression, proving a means for discovery of cis-acting regulatory factors with potential clinical relevance.

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Non-coding RNAs match the deleted genomic regions in humans.

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Non-coding RNAs match the deleted genomic regions in humans.

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