Long noncoding RNA PAHAL modulates locust behavioural plasticity through the feedback regulation of dopamine...

Some long noncoding RNAs (lncRNAs) are specifically expressed in brain cells, implying their neural and behavioural functions. However, how lncRNAs contribute to neural regulatory networks governing the precise behaviour of animals is less explored. Here, we report the regulatory mechanism of the nuclear-enriched lncRNA PAHAL for dopamine biosynthesis and behavioural adjustment in migratory locusts (Locusta migratoria), a species with extreme behavioral plasticity. PAHAL is transcribed from the sense (coding) strand of the gene encoding phenylalanine hydroxylase (PAH), which is responsible for the synthesis of dopamine from phenylalanine. PAHAL positively regulates PAH expression resulting in dopamine production in the brain. In addition, PAHAL modulates locust behavioral aggregation in a population density-dependent manner. Mechanistically, PAHAL mediates PAH transcriptional activation by recruiting serine/arginine-rich splicing factor 2 (SRSF2), a transcription/splicing factor, to the PAH proximal promoter. The co-activation effect of PAHAL requires the interaction of the PAHAL/SRSF2 complex with the promoter-associated nascent RNA of PAH. Thus, the data support a model of feedback modulation of animal behavioural plasticity by an lncRNA. In this model, the lncRNA mediates neurotransmitter metabolism through orchestrating a local transcriptional loop.