LncRNAs – macromolecules with big roles in neurobiology and neurological diseases

Long noncoding RNAs (lncRNAs) are recently defined as thousands of RNA molecules longer than 200 nucleotides and lacking an appreciable open reading frame in mammals. Although lncRNAs lack protein-coding function, they play critical roles in the regulation of almost all the protein-coding genes in a cell at various stages including chromatin modification, transcription and post-transcriptional processing. It is thus not surprising that lncRNAs may be the crucial regulators in the normal development, physiology and pathology. LncRNAs in neuroscience is a novel research field. Interestingly, recent studies have demonstrated that many lncRNAs are highly expressed in brain and their dysregulations occur in neurological disorders. LncRNAs could be novel biomarkers and could be potential new targets for new drugs for many neurological diseases in the future, although the related studies are still at in the early stages.

Paradigm for the mechanisms of lncRNAs functions

Transcription from an upstream noncoding promoter (tawny) can negatively or positively affect the downstream gene expression (purple) via transcriptional interference through inhibiting RNA polymerase II recruitment (1), or via inducing chromatin remodeling and histone modifications (2),respectively. Additionally, antisense transcripts (blue) are able to hybridize to their specific sense transcripts (purple), resulting in alternatively spliced transcript (3) or various endogenous siRNAs(4). With binding to specific protein partners(green), a noncoding transcript can modulate the activity of the protein(5), or allow the formation of a larger RNA–protein complex(6), or alter the cellular localization of the protein(7). LncRNAs (yellow) can be processed to yield small RNAs including miRNAs, piRNAs and others (8). Moreover, they can also act as miRNA sponges that affect the competitive endogenous RNAs(9)