Temporal transcriptome analysis of neuronal commitment reveals the preeminent role of the divergent lncRNA biotype and a critical candidate gene during differentiation

Abstract

lncRNA genes can be genic or "intergenic". "Genic" RNAs can be further divided into six biotypes. Through genomewide analysis of a publicly available data set on corticogenesis, we found that the divergent lncRNA (XH) biotype, comprising the lncRNA and the coding gene being in opposite directions in a head-to-head manner, was most prominent during neural commitment. Within this biotype, a coding gene/divergent RNA pair of the BASP1 gene and the uncharacterized RNA loc285696 (hitherto referred as BASP1-AS1) formed a major HUB gene during neuronal differentiation. Experimental validation during the in vitro differentiation of human neural progenitor cells (hNPCs) showed that BASP1-AS1 regulates the expression of its adjacent coding gene, BASP1. Both transcripts increased sharply on the first day of neuronal differentiation of hNPCs, to fall steadily thereafter, reaching very low levels in differentiated neurons. BASP1-AS1 RNA and the BASP1 gene formed a molecular complex that also included the transcription factor TCF12. TCF12 is coded by the DYX1 locus, associated with inherited dyslexia and neurodevelopmental defects. Knockdown of BASP1-AS1, BASP1, or TCF12 impaired the neuronal differentiation of hNPCs, as seen by reduction in DCX and TUJ1-positive cells and by reduced neurite length. There was also increased cell proliferation. A common set of critical genes was affected by the three molecules in the complex. Our study thus identified the role of the XH biotype and a novel mediator of neuronal differentiation-the complex of BASP1-AS1, BASP1, and TCF12. It also linked a neuronal differentiation pathway to inherited dyslexia.

LncRNA BASP1‐AS1 interacts with YBX1 to regulate Notch transcription and drives the malignancy of melanoma

“…At present, only BASP1‐AS1 regulates BASP1 in hNPCs and plays a crucial role in neuronal differentiation. 19 The importance of BASP1‐AS1 in the progression and prognosis of melanoma is still unclear. In this study, we used the subcellular stratification technique to find that BASP1‐AS1 was localized in the nucleus, suggesting that BASP1‐AS1 may be involved in the transcription process.…”

“…Survival analysis showed that functional LncRNAs‐CNV might be a candidate prognostic biomarker for clinical application, and BASP1 ‐AS1 is a new LncRNA that has not been screened out in melanoma, even if it has been found that BASP1‐AS1 regulates BASP1 in HNPCs and plays a key role in neuronal differentiation. 19 …”

“…We used prognostic‐related coding genes, CNV, and methylation sites, and selected 366 samples shared by the three omics to conduct a multigroup clustering analysis to construct a prognostic model of four genes in the TCGA cohort, which was verified by http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65904. Survival analysis showed that functional LncRNAs‐CNV might be a candidate prognostic biomarker for clinical application, and BASP1 ‐AS1 is a new LncRNA that has not been screened out in melanoma, even if it has been found that BASP1‐AS1 regulates BASP1 in HNPCs and plays a key role in neuronal differentiation 19 …”

“…Survival analysis showed that functional LncRNAs-CNV might be a candidate prognostic biomarker for clinical application, and BASP1-AS1 is a new LncRNA that has not been screened out in melanoma, even if it has been found that BASP1-AS1 regulates BASP1 in HNPCs and plays a key role in neuronal differentiation. 19 YBX1 (Y box binding protein 1) is an RNA/DNA binding multifunctional protein, which is recognized as a carcinogenic transcription factor that can regulate apoptosis, translation, cell proliferation, mRNA splicing, repair, differentiation, and the stress response. 20 Additionally, studies have shown that the LncRNA DSCAM-AS1 interacts with YBX1 to promote cancer progression by forming a positive feedback loop that activates the FOXA1 transcription network.…”

Association between the expression of lncRNA BASP-AS1 and volume of right hippocampal tail moderated by episode duration in major depressive disorder: a CAN-BIND 1 report

“…Although the exact physiological role of BASP1-AS1 in the brain is not fully understood, it could regulate the expression of BASP1. Indeed, a recent study, Prajapati et al highlighted, in "in vitro" model, that BASP1-AS1 regulates BASP1 in human neural progenitor cells, and has a critical role in neuronal differentiation [57]. It seemed that over-expression of BASP1 in adult neurons promotes sprouting [58] and, more specifically, modulate neurite outgrowth in hippocampal neurons [59].…”