The role of human-specific, transposon-controlled lncRNAs in brain development

The increased complexity of the human brain has resulted in a new level of cognitive functions. However, the genetic alterations underlying this complexity remain largely unknown.

A large portion of genetic information specific to humans is stored in transposable elements (TEs), that make up around 50% of the human genome.

This project is based on the hypothesis that TEs have played a key role in the evolution of the human brain by acting as a source of regulatory elements.

We have in preliminary experiments identified two human-specific lncRNAs, LINC00662 and LINC01876, that are regulated by species-specific TE-insertions.To investigate how these two non-coding RNAs contribute to brain development we will use CRISPR-approaches to silence lncRNAs and investigate the consequence on the transcriptome and epigenome.

We will use cerebral organoids to investigate the functional role of the lncRNAs in human brain development.

Finally, we will use novel biochemical methods to explore the mechanisms underpinning how the two lncRNAs control transcriptional and post-transcriptional programs.This project is a concentrated effort to understand the role of two lncRNAs under the control of species-specific TE insertions.

TEs represent a poorly characterized class of genetic elements and this research will transform our understanding of the genetic basis for the human brain. This research will also generate much-needed new hypotheses on the etiology and pathology of psychiatric disorders.