A systematic review of non-coding RNA genes with differential expression profiles associated with autism spectrum disorders

Abstract

Aims To identify differential expression of shorter non-coding RNA (ncRNA) genes associated with autism spectrum disorders (ASD). Background ncRNA are functional molecules that derive from non-translated DNA sequence. The HUGO Gene Nomenclature Committee (HGNC) have approved ncRNA gene classes with alignment to the reference human genome. One subset is microRNA (miRNA), which are highly conserved, short RNA molecules that regulate gene expression by direct post-transcriptional repression of messenger RNA. Several miRNA genes are implicated in the development and regulation of the nervous system. Expression of miRNA genes in ASD cohorts have been examined by multiple research groups. Other shorter classes of ncRNA have been examined less. A comprehensive systematic review examining expression of shorter ncRNA gene classes in ASD is timely to inform the direction of research. Methods We extracted data from studies examining ncRNA gene expression in ASD compared with non-ASD controls. We included studies on miRNA, piwi-interacting RNA (piRNA), small NF90 (ILF3) associated RNA (snaR), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), transfer RNA (tRNA), vault RNA (vtRNA) and Y RNA. The following electronic databases were searched: Cochrane Library, EMBASE, PubMed, Web of Science, PsycINFO, ERIC, AMED and CINAHL for papers published from January 2000 to May 2022. Studies were screened by two independent investigators with a third resolving discrepancies. Data was extracted from eligible papers. Results Forty-eight eligible studies were included in our systematic review with the majority examining miRNA gene expression alone. Sixty-four miRNA genes had differential expression in ASD compared to controls as reported in two or more studies, but often in opposing directions. Four miRNA genes had differential expression in the same direction in the same tissue type in at least 3 separate studies. Increased expression was reported in miR-106b-5p, miR-155-5p and miR-146a-5p in blood, post-mortem brain, and across several tissue types, respectively. Decreased expression was reported in miR-328-3p in bloods samples. Seven studies examined differential expression from other classes of ncRNA, including piRNA, snRNA, snoRNA and Y RNA. No individual ncRNA genes were reported in more than one study. Six studies reported differentially expressed snoRNA genes in ASD. A meta-analysis was not possible because of inconsistent methodologies, disparate tissue types examined, and varying forms of data presented. Conclusion There is limited but promising evidence associating the expression of certain miRNA genes and ASD, although the studies are of variable methodological quality and the results are largely inconsistent. There is emerging evidence associating differential expression of snoRNA genes in ASD. It is not currently possible to say whether the reports of differential expression in ncRNA may relate to ASD aetiology, a response to shared environmental factors linked to ASD such as sleep and nutrition, other molecular functions, human diversity, or chance findings. To improve our understanding of any potential association, we recommend improved and standardised methodologies and reporting of raw data. Further high-quality research is required to shine a light on possible associations, which may yet yield important information.

piRNAs in the human retina and retinal pigment epithelium reveal a potential role in intracellular trafficking and oxidative stress

“…These four piRNAs were found to have association with neuronal diseases, including Alzheimers' disease 42 and autism spectrum disorder. 43,44 Among the evaluated piRNAs, piR-hsa-1207 and piR-hsa-24683 were expressed more in the retina compared to RPE, which was in accordance with their CpM values from the RNA-seq data. Next, we checked the 3 0 -terminal 2 0 -O-methylation of piRNA via RTL-P analysis to elucidate their characteristic sequence feature.…”

A bibliometric analysis of autism spectrum disorder signaling pathways research in the past decade

“…Recent trends in research also highlight the profound impact of technological advancements on ASD studies. Advancements in techniques such as single-cell RNA sequencing ( 65 ), brain imaging technologies [such as fMRI ( 66 ) and MEG ( 67 )], and genomics, among others, have provided us with opportunities for a deeper understanding of the mechanisms and characteristics of ASD.…”