Large-scale sequencing projects such as ENCODE and FANTOM have been demonstrating that the majority of the mammalian genome is transcribed. This generates a vast repertoire of transcripts that includes long non-coding RNA (lncRNA) and transcribed repetitive sequences. Surprisingly, the large majority of genes share their genomic region with another gene on the opposite filament forming Sense/Antisense pairs (S/AS). Massive antisense transcription seems to be a common feature of cells ranging from human to drosophila.
Gustincich's group recently identified AS Uchl1 as a nuclear-enriched long noncoding RNA (lncRNA) antisense to Uchl1/Park5 that is specifically expressed in dopaminergic neurons. We have then showed that AS Uchl1 increases UchL1 protein synthesis at post-transcriptional level. AS Uchl1 activity depends on the presence of a 5’ overlapping sequence and an embedded inverted SINEB2 repetitive element. In addition, mTORc1 inhibition by the neuroprotective molecule rapamycin causes an increase in UchL1 protein that is associated to shuttling of AS Uchl1 RNA from the nucleus to the cytoplasm and recruitment of the overlapping sense protein-encoding mRNA to active polysomes for translation. Thus, AS Uchl1 is the first identified lncRNA able to stimulate translation of specific mRNAs, in conditions in which CAP-dependent translation is reduced.
AS Uchl1 is considered the representative member of a new functional class of natural and synthetic lncRNAs that activate translation. Gustincich's group have called this class SINEUP since, by the function of a SINE sequence, these RNAs are able to UP-regulate translation of sense mRNAs, and is currently investigating the physiological role of natural SINEUPs in brain function.