Identification and function of long non-coding RNA

Abstract

Long non-coding (lnc) RNAs are defined as non-protein coding RNAs distinct from housekeeping RNAs such as tRNAs, rRNAs, and snRNAs, and independent from small RNAs with specific molecular processing machinery such as micro- or piwi-RNAs. Recent studies of lncRNAs across different species have revealed a diverse population of RNA molecules of differing size and function. RNA sequencing studies suggest transcription throughout the genome, so there is a need to understand how sequence relates to functional and structural relationships amongst RNA molecules. Our synthesis of recent studies suggests that neither size, presence of a poly-A tail, splicing, direction of transcription, nor strand specificity are of importance to lncRNA function. Rather, relative genomic position in relation to a target is fundamentally important. In this review, we describe issues of key importance in functional assessment of lncRNA and how this might apply to lncRNAs important in neurodevelopment.

Keywords: epigenetics; gene regulation; neurodevelopment; non-coding RNA.

FIGURE 1

Different mechanistic action of lncRNAs that overlap an mRNA target. (A) lncRNA expressed from the antisense strand may have an overlapping domain, providing specificity, and a non-overlapping activation domain. This activation domain could be a sequence that allows single-strand binding for different molecules, leading to stabilization or degradation of the RNA:RNA complex. (B) Complementary binding of overlapping mRNA and lncRNA could create a double-stranded binding site for protein binding, leading to selective degradation of stabilization of the RNA:RNA complex.