Another, post-transcriptional, mechanism of regulation of splicing may be represented by lncRNAs. Spliceosome represents gigantic machinery consisting of snRNAs and splicing factors and functionally coupled with gene expression38. Since lncRNAs can interact with DNA, RNA, and proteins, it is possible that they serve as a master regulator of the spliceosome. We interrogated lncRNAs and found that lncRNAs affected in AUD were functionally related to splicing. Recent evidence indicates that even individual lncRNA may cause marked changes in splicing. Thus, lncRNA MALAT1 which is upregulated in the brain of alcoholics39 interacted with splicing factors HNRNPF and HNRNPF1, changed levels of serine–arginine-rich splicing factors, and affected alternative splicing of hundreds of transcripts40. Alternative splicing was documented to be regulated by sno-lncRNAs, lncRNA flanked by small nucleolar RNA (snoRNAs)41 which are a family of conserved nuclear RNAs located in Cajal bodies or nucleoli and participating in snRNAs modifications. Several lncRNAs are able to interact with specific splicing factors42. A new exciting field is represented by circular RNAs (circRNAs), covalently closed single-stranded RNA complexes arising from backsplicing. These complexes are highly stable, and it is speculated that they might be capable of competing with pre-mRNA for spliceosome43.
