Abstract
Accumulating evidence indicates noncoding RNAs (ncRNAs) fine-tune gene expression with mysterious machinery. We conducted a combination of mRNA, miRNA, circRNA, LncRNA microarray analyses on 10 adults' lumbar discs. Moreover, we performed additional global exploration on RNA interacting machinery in terms of in silico computational pipeline. Here we show the landscape of RNAs in human lumbar discs. In general, the RNA-abundant landscape comprises 14,635 mRNAs (37.93%), 2,059 miRNAs (5.34%), 18,995 LncRNAs (49.23%) and 2,894 (7.5%) circRNAs. Chromosome 1 contributes for RNA transcription at most (10%). Bi-directional transcription contributes evenly for RNA biogenesis, in terms of 5′ to 3′ and 3′ to 5′. Despite the majority of circRNAs are exonic, antisense (1.49%), intergenic (0.035%), intragenic (1.69%), and intronic (6.29%) circRNAs should not be ignored. A single miRNA could interact with a multitude of circRNAs. Notably, CDR1as or ciRS-7 harbors 66 consecutive binding sites for miR-7-5p (previous miR-7), evidencing our pipeline. The majority of binding sites are perfect-matched (78.95%). Collectively, global landscape of RNAs sheds novel insights on RNA interacting mechanisms in human intervertebral disc degeneration.
Highlights
Intervertebral disc degeneration (IDD) is the chief contributing factor to low back pain with deleterious medical and social impact [1]
We conducted a combination of mRNA, miRNA, circRNA, long ncRNAs (LncRNAs) microarray analyses on 10 adults’ lumbar discs
Human lumbar discs are RNA-abundant, the expression profiling of which comprise 14,635 mRNAs out of 30215 protein-coding transcripts (37.93%, Supplementary Table S1), 2,059 miRNAs (5.34%, Supplementary Table S2), 18,995 LncRNAs (49.23%, Supplementary Table S3) and 2,894 circRNAs (7.5%, Supplementary Table S4). mRNAs account for 37.93% of total RNAs; whereas noncoding RNAs (ncRNAs) account for 62.07% of total RNAs (Figure 1J). mRNAs and LncRNAs account for the majority of RNA splicing products (87.16%)
Summary
Intervertebral disc degeneration (IDD) is the chief contributing factor to low back pain with deleterious medical and social impact [1]. Increasing evidence reveals that IDD is a multifaceted spinal disease. Both genetic and environmental factors contribute to IDD, the chief of which are genetics [2, 3]. The genetics machinery ranges from single-nucleotide variants [4] and coding genes [5,6,7,8], to newly defined noncoding RNAs (ncRNAs). Recent whole-genome sequencing (WGS) studies have greatly expanded our scopes upon human genome [9, 10]. As a multitude set of transcript products of the human genome, ncRNAs account for 98% of the human genome devoid of protein-coding function. NcRNAs play critical roles in a variety of biological processes pertaining to gene expression [11, 12]
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