Neuropeptide Y: Identification of a novel rat mRNA splice-variant that is downregulated in the hippocampus and the prefrontal cortex of a depression-like model

► The rat Npy mRNA exists in two splice-variants. ► The two Npy variants share the same transcription start site. ► The “short”Npy mRNA does not seem to code for a protein. ► The “short”Npy mRNA is expressed in lower levels than the “long” one. ► Both Npy mRNAs are decreased in a genetic model of depression. Neuropeptide Y (NPY) is known to influence emotional processing and decreased NPY levels have been associated with mood and anxiety disorders. Alternative splicing of pre-messenger RNA is a cellular mechanism that allows for transcriptome diversity, yet there is limited knowledge in this respect with regard to Npy. Since the hippocampus and the prefrontal cortex play an important role in affective disorders, we investigated alternative splicing of Npy in these regions of a rat model of depression (Flinders Sensitive Line, FSL) and its controls (Flinders Resistant Line, FRL). The existence of different Npy messenger RNA (mRNA) variants was examined using 5′ and 3′ RACE. In addition to the Npy mRNA species annotated in GenBank and Ensembl, we identified a novel “short” mRNA splice variant. Immunoblotting results argued against a putative translation of this “short” mRNA into protein in brain tissue. Compared to the FRL, the FSL had reduced “short”Npy mRNA levels in the HIP (P=0.00014) and the PFC (P=0.016). Gene expression analyses in five brain regions of an outbred rat strain supported the presence of the “short”Npy transcript in all examined regions and showed that it is expressed in ∼2.4-fold lower levels than the “long”Npy mRNA. Finally, sequencing of the 5′ RACE products revealed a transcription start site of Npy that is different from the currently annotated position. These data add to the characterization of the rat Npy mRNA and demonstrate the presence of a novel transcript with a so far unknown function.