The Human Developing Cerebral Cortex Is Characterized by an Elevated De Novo Expression of Long Noncoding RNAs in Excitatory Neurons

Autor(es)

Morales-Vicente, David A. ; Tahira, Ana C. ; Woellner-Santos, Daisy ; Amaral, Murilo S. ; Berzoti-Coelho, Maria G. ; Verjovski-Almeida, Sergio

• Tipo de documento: Artigo Científico
• Fonte: Molecular Biology and Evolution; v. 41, n. 7, p. 24-pg., 2024-07-03.

Resumo

The outstanding human cognitive capacities are computed in the cerebral cortex, a mammalian-specific brain region and the place of massive biological innovation. Long noncoding RNAs have emerged as gene regulatory elements with higher evolutionary turnover than mRNAs. The many long noncoding RNAs identified in neural tissues make them candidates for molecular sources of cerebral cortex evolution and disease. Here, we characterized the genomic and cellular shifts that occurred during the evolution of the long noncoding RNA repertoire expressed in the developing cerebral cortex and explored putative roles for these long noncoding RNAs in the evolution of the human brain. Using transcriptomics and comparative genomics, we comprehensively annotated the cortical transcriptomes of humans, rhesus macaques, mice, and chickens and classified human cortical long noncoding RNAs into evolutionary groups as a function of their predicted minimal ages. Long noncoding RNA evolutionary groups showed differences in expression levels, splicing efficiencies, transposable element contents, genomic distributions, and transcription factor binding to their promoters. Furthermore, older long noncoding RNAs showed preferential expression in germinative zones, outer radial glial cells, and cortical inhibitory (GABAergic) neurons. In comparison, younger long noncoding RNAs showed preferential expression in cortical excitatory (glutamatergic) neurons, were enriched in primate and human-specific gene co-expression modules, and were dysregulated in neurodevelopmental disorders. These results suggest different evolutionary routes for older and younger cortical long noncoding RNAs, highlighting old long noncoding RNAs as a possible source of molecular evolution of conserved developmental programs; conversely, we propose that the de novo expression of primate- and human-specific young long noncoding RNAs is a putative source of molecular evolution and dysfunction of cortical excitatory neurons, warranting further investigation. (AU)

• Processo FAPESP: 20/02976-9 - Caracterização dos sítios de interação no genoma do lincRNA PVT1 associado ao receptor de andrógeno em linhagem de Câncer de Próstata
• Beneficiário: Maria Gabriela Berzoti Coelho
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/09404-3 - Identificação por meio de phage display com biblioteca sintética de cDNAs dos epítopos antigênicos de Schistosoma mansoni alvejados pela resposta imune de macacos Rhesus (Macaca mulatta) infectados pelo parasita e autocurados
• Beneficiário: Daisy Woellner Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 18/23693-5 - Mecanismos de ação de RNAs longos não-codificadores envolvidos nos programas de ativação gênica em eucariotos
• Beneficiário: Sergio Verjovski Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Temático