The increased application of transcriptome-wide profiling approaches has led to an explosion in the number of documented long non-coding RNAs (lncRNAs). While these new and enigmatic players in the complex transcriptional milieu are encoded by a significant proportion of the genome, their functions are mostly unknown. Early discoveries support a paradigm in which lncRNAs regulate transcription via chromatin modulation, but new functions are steadily emerging. Given the biochemical versatility of RNA, lncRNAs may be used for various tasks, including post-transcriptional regulation, organization of protein complexes, cell-cell signalling and allosteric regulation of proteins.

SUMMARY High-throughput gene expression analysis has revealed a plethora of previously undetected transcripts in eukaryotic cells. In this study we investigate >1100 unannotated transcripts in yeast predicted to lack protein-coding capacity. We show that a majority of these RNAs are enriched on polyribosomes akin to mRNAs. Ribosome profiling demonstrates that many bind translocating ribosomes within predicted open-reading frames 10–96 codons in size. We validate expression of peptides encoded within a subset of these RNAs and provide evidence for conservation among yeast species. Consistent with their translation, many of these transcripts are targeted for degradation by the translation-dependent, nonsense-mediated RNA decay (NMD) pathway. We identify lncRNAs also sensitive to NMD, indicating translation of non-coding transcripts also occurs in mammals. These data demonstrate transcripts considered to lack coding potential are bona fide protein-coding, and expand the proteome of yeast and possibly other eukaryotes.

Summary Decapping represents a critical control point in regulating expression of protein coding genes. Here we demonstrate that decapping also modulates expression of long non-coding RNAs (lncRNAs). Specifically, levels of >100 lncRNAs in yeast are controlled by decapping and are degraded by a pathway that occurs independent of decapping regulators. We find many lncRNAs degraded by DCP2 are expressed proximal to inducible genes. Of these, we show several genes required for galactose utilization are associated with lncRNAs that have expression patterns inversely correlated with their mRNA counterpart. Moreover, decapping of these lncRNAs is critical for rapid and robust induction of GAL gene expression. Failure to destabilize a lncRNA known to exert repressive histone modifications results in perpetuation of a repressive chromatin state that contributes to reduced plasticity of gene activation. We propose that decapping and lncRNA degradation serve a vital role in transcriptional regulation specifically at inducible genes.

Intricate layers of regulation determine the unique gene expression profiles of a given cell and, therefore, underlie the immense phenotypic diversity observed among cell types. Understanding the mechanisms that govern which genes are expressed and which genes are silenced is a fundamental focus in biology. The Polycomb and Trithorax group chromatin proteins play important roles promoting the stable and heritable repression and activation of gene expression, respectively. These proteins, which are conserved across metazoans, modulate post-translational modifications on histone tails and regulate nucleosomal structures. Here, we review recent advances that have shed light on the mechanisms by which these two classes of proteins act to maintain epigenetic memory and allow dynamic switches in gene expression during development.