The phrase “natural born leader” is often used to describe those among us with a tendency to dominate, boss, and—put simply—win in life. Newly published research from the Huazhong University of Science and Technology (China) and Boston University (USA) may have demonstrated a molecular truth to this expression.

Authors Mei Ma, Wan Xiong and Fan Hu—lead by Professors Dan Liu and Ling-Qiang Zhu—aimed to elucidate precisely what underlies gaining the upper hand in society; specifically, the pathways by which long non-coding RNA (lncRNA) might regulate epigenetic changes previously observed in dominant animals with a history outcompeting their rivals.

Ma et al. found that one lncRNA species in particular, AtLAS, was crucial in controlling social hierarchy in mice—particularly in the medial prefrontal cortex (mPFC). AtLAS was naturally increased in the submissive and decreased in the dominant; therein, the silencing or over expression of AtLAS appears to be implicated in social rank. Using Norgen's Cytoplasmic and Nuclear RNA Purification Kit (21000), the authors were able to determine that AtLAS was primarily lost from the nuclear fraction of mPFC neurons in dominant mice, further suggesting a role for AtLAS in epigenetic regulation.

The authors showed this to be polyadenylation of its target gene, Synapsin II (Syn2), thereby altering the production and ratios of translated Syn2a and Syn2b, which impacts post-synaptic AMPA receptor (AMPAR) trafficking—a molecular pathway implicated in synapse and behaviour formation and modification. Ma et al. proposed that with increased AtLAS, production of Syn2b increased, subsequently binding AMPARs, reducing membrane insertion for excitatory synaptic transmission, and ultimately driving a submissive phenotype. Conversely, reducing AtLAS and therefore reducing Synb2—and, in fact, simply reducing Syn2b directly—appeared to increase AMPAR insertion, enhancing synaptic efficiency and leading to social dominance.

With an intricate proposed mechanism supported by the authors’ findings and previously published work, Ma et al. then engineered a peptide to impede direct Syn2b-AMPAR binding and favour synaptic strength and social ascendance. This synthetic peptide, P-2B, was shown to work in mice via intraperitoneal injection, and may hold promise as a treatment for animal and human synaptic disorders such as schizophrenia.

Figure 1. Proposed working model of AtLAS-syn2b in establishing social hierarchy status (Ma et al. 2020).