Defining the biological functions of long non-coding RNAs, individually or as a class, and teasing apart the role of underlying genomic sequences remains the biggest challenge for this field.

Ribosome profiling data from several eukaryotic species provides strong evidence that many long non-coding RNA molecules encode novel short proteins.

The identification of a SUMO E3 ligase engaged in lncRNA transcription, subsequently leading to target-directed small RNA degradation, reveals an unexplored layer of regulatory mechanisms within small RNA-directed chromatin regulation.

LncRNA Neat1, with paraspeckle proteins, controls translational induction of (lymph)angiogenic and cardioprotective factors by the IRES-dependent mechanism in mouse cardiomyocytes submitted to hypoxia.

Genome-wide identification of long non-coding RNAs produced by RNA Polymerase V identifies their role in heterochromatin maintenance on the boundaries of repressed regions.

Phenomics assays reveal hundreds of mutant phenotypes for long non-coding RNAs grown in specific environmental or physiological contexts, indicating that most of these RNAs exert cellular functions under certain conditions.

Mitochondrial energy metabolism is post-transcriptionally regulated through an interplay between long and short non-coding RNAs.

A novel long non-coding RNA targets microRNA miR-34a for epigenetic silencing and initiates asymmetric division of colon cancer stem cells.

Dali regulates transcription of the Pou3f3 locus locally and binds and regulates active promoters in trans by modulating DNA methylation status.

A non-coding RNA-based targeting mechanism could potentially epigenetically maintain specialized chromatin structures, such as the centromere, in vivo.