THE HIDDEN TRANSLATION OF SOCIAL FEAR: UNCOVERING MICROPROTEIN CANDIDATES

Social fear is a defining feature of social anxiety disorder, a prevalent psychiatric condition that severely impairs social functioning. Despite its clinical relevance, the neurobiological mechanisms underlying social fear learning and extinction remain incompletely understood. While protein-coding genes have been extensively studied in fear-related circuits, the potential contribution of microproteins encoded by previously annotated non-coding RNAs has largely been overlooked. Here, we investigate whether such microproteins may be involved in the acquisition or extinction of social fear.
Using social fear conditioning in mice, we combined Translating Ribosome Affinity Purification (TRAP) with RNA sequencing to profile actively translated transcripts in neurons of the paraventricular nucleus of the hypothalamus (PVN) and the septum. Across comparisons of conditioned and unconditioned animals following acquisition or extinction, we identified approximately 150 transcripts showing robust differential expression, defined by a minimum twofold change. Notably, many of these transcripts are currently annotated as non-coding RNAs. Their association with ribosomes suggests that they may contain previously unrecognized open reading frames and represent microprotein-encoding candidates.
To explore this possibility further, we are establishing complementary mass spectrometry–based approaches and in vitro assays to assess translation and cellular function of selected candidate sequences. Together, these preliminary findings point to a previously underexplored molecular layer in social fear–related circuits and provide a foundation for future studies on the role of microproteins in socio-emotional dysfunctions.