Genome-wide analysis of long noncoding RNA stability

Transcriptomic analyses have identified tens of thousands of intergenic, intronic, and cis-antisense long noncoding RNAs (IncRNAs) that are expressed from mammalian genomes. Despite progress in functional characterization, little is known about the post-transcriptional regulation of IncRNAs and their half-lives. Although many are easily detectable by a variety of techniques, it has been assumed that IncRNAs are generally unstable, but this has not been examined genome-wide. Utilizing a custom noncoding RNA array, we determined the half-lives of similar to 800 IncRNAs and similar to 12,000 mRNAs in the mouse Neuro-2a cell line. We find only a minority of IncRNAs are unstable. LncRNA half-lives vary over a wide range, comparable to, although on average less than, that of mRNAs, suggestive of complex metabolism and widespread functionality. Combining half-lives with comprehensive IncRNA annotations identified hundreds of unstable (half-life < 2 h) intergenic, cis-antisense, and intronic IncRNAs, as well as IncRNAs showing extreme stability (half-life > 16 h). Analysis of IncRNA features revealed that intergenic and cis-antisense RNAs are more stable than those derived from introns, as are spliced IncRNAs compared to unspliced (single exon) transcripts. Subcellular localization of IncRNAs indicated widespread trafficking to different cellular locations, with nuclear-localized IncRNAs more likely to be unstable. Surprisingly, one of the least stable IncRNAs is the well-characterized paraspeckle RNA Neat!, suggesting Neat! instability contributes to the dynamic nature of this subnuclear domain. We have created an online interactive resource (http://stability.matticklab.com) that allows easy navigation of IncRNA and mRNA stability profiles and provides a comprehensive annotation of 7200 mouse IncRNAs.