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

Autor:	Morales-Vicente DA; Laboratório de Ciclo Celular, Instituto Butantan, São Paulo, Brazil.; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil., Tahira AC; Laboratório de Ciclo Celular, Instituto Butantan, São Paulo, Brazil., Woellner-Santos D; Laboratório de Ciclo Celular, Instituto Butantan, São Paulo, Brazil.; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil., Amaral MS; Laboratório de Ciclo Celular, Instituto Butantan, São Paulo, Brazil., Berzoti-Coelho MG; Laboratório de Ciclo Celular, Instituto Butantan, São Paulo, Brazil.; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil., Verjovski-Almeida S; Laboratório de Ciclo Celular, Instituto Butantan, São Paulo, Brazil.; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Molecular biology and evolution [Mol Biol Evol] 2024 Jul 03; Vol. 41 (7).
DOI:	10.1093/molbev/msae123
Abstrakt:	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. Competing Interests: Conflict of Interest All authors declare that there are no financial or non-financial competing interests related to this work. (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)
Databáze:	MEDLINE
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