LINE-1 regulates cortical development by acting as long non-coding RNAs

Damiano Mangoni, Alessandro Simi, Pierre Lau, Alexandros Armaos, Federico Ansaloni, Azzurra Codino, Devid Damiani, Lavinia Floreani, Valerio Carlo, Diego Vozzi, Francesca Persichetti, Claudio Santoro, Luca Pandolfini, Gian Gaetano Tartaglia, Remo Sanges () and Stefano Gustincich ()
Additional contact information
Damiano Mangoni: Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT)
Alessandro Simi: Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT)
Pierre Lau: Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT)
Alexandros Armaos: Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT)
Federico Ansaloni: Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT)
Azzurra Codino: Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT)
Devid Damiani: Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT)
Lavinia Floreani: Area of Neuroscience, International School for Advanced Studies (SISSA)
Valerio Carlo: Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT)
Diego Vozzi: Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT)
Francesca Persichetti: University of Piemonte Orientale (UPO)
Claudio Santoro: University of Piemonte Orientale (UPO)
Luca Pandolfini: Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT)
Gian Gaetano Tartaglia: Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT)
Remo Sanges: Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT)
Stefano Gustincich: Central RNA Laboratory, Istituto Italiano di Tecnologia (IIT)

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Long Interspersed Nuclear Elements-1s (L1s) are transposable elements that constitute most of the genome’s transcriptional output yet have still largely unknown functions. Here we show that L1s are required for proper mouse brain corticogenesis operating as regulatory long non-coding RNAs. They contribute to the regulation of the balance between neuronal progenitors and differentiation, the migration of post-mitotic neurons and the proportions of different cell types. In cortical cultured neurons, L1 RNAs are mainly associated to chromatin and interact with the Polycomb Repressive Complex 2 (PRC2) protein subunits enhancer of Zeste homolog 2 (Ezh2) and suppressor of zeste 12 (Suz12). L1 RNA silencing influences PRC2’s ability to bind a portion of its targets and the deposition of tri-methylated histone H3 (H3K27me3) marks. Our results position L1 RNAs as crucial signalling hubs for genome-wide chromatin remodelling, enabling the fine-tuning of gene expression during brain development and evolution.

Date: 2023
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DOI: 10.1038/s41467-023-40743-7

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