Genome-wide differential expression of synaptic long noncoding RNAs in autism spectrum disorder

Abstract

A genome-wide differential expression of long noncoding RNAs (lncRNAs) was identified in blood specimens of autism spectrum disorder (ASD). A total of 3929 lncRNAs were found to be differentially expressed in ASD peripheral leukocytes, including 2407 that were upregulated and 1522 that were downregulated. Simultaneously, 2591 messenger RNAs (mRNAs), including 1789 upregulated and 821 downregulated, were also identified in ASD leukocytes. Functional pathway analysis of these lncRNAs revealed neurological pathways of the synaptic vesicle cycling, long-term depression and long-term potentiation to be primarily involved. Thirteen synaptic lncRNAs, including nine upregulated and four downregulated, and 19 synaptic mRNAs, including 12 upregulated and seven downregulated, were identified as being differentially expressed in ASD. Our identification of differential expression of synaptic lncRNAs and mRNAs suggested that synaptic vesicle transportation and cycling are important for the delivery of synaptosomal protein(s) between presynaptic and postsynaptic membranes in ASD. Finding of 19 lncRNAs, which are the antisense, bi-directional and intergenic, of HOX genes may lead us to investigate the role of HOX genes involved in the development of ASD. Discovery of the lncRNAs of SHANK2-AS and BDNF-AS, the natural antisense of genes SHANK2 and BDNF, respectively, indicates that in addition to gene mutations, deregulation of lncRNAs on ASD-causing gene loci presents a new approach for exploring possible epigenetic mechanisms underlying ASD. Our study also opened a new avenue for exploring the use of lncRNA(s) as biomarker(s) for the early detection of ASD.

A Point Mutation in a lincRNA Upstream of GDNF Is Associated to a Canine Insensitivity to Pain: A Spontaneous Model for Human Sensory Neuropathies

“…Moreover, BDNF interacts with the TrkB receptor encoded by the NTRK2 gene, which has a paralog NTRK1 , already annotated as mutated in HSAN type IV [5,56,57]. In addition, it has been shown that the inhibition of BDNF-AS increases BDNF levels in vivo [38,58]. Modarresi et al recently showed that the knock-out of GDNF-AS increases the expression level of GDNF in human HEK293T cells [59].…”

The link between long noncoding RNAs and depression

“…Recently, genome-wide studies identified thousand lncRNAs to be aberrantly expressed in peripheral leukocytes of ASD patients (Wang et al, 2015) as well as in ASD brain tissues (Ziats and Rennert, 2013). A comprehensive analysis of lncRNA co-expression relationships in drug-naive first-episode early-onset schizophrenia (EOS) patients showed that convergent lncRNA alteration may be involved in the etiologies of EOS (Ren et al, 2015).…”

Tetracycline-inducible shRNA targeting antisense long non-coding RNA HIF1A-AS2 represses the malignant phenotypes of bladder cancer

“…With the rapid development of sequencing technologies [5], a series of dysregulated long non-coding RNAs (lncRNAs) have been found in many human diseases [6,7], especially in cancers [8,9]. Accumulating evidences suggested that long non-coding RNAs (lncRNAs) perform important or vital functions in the malignant tumors [10,11].…”