MATR3-antisense LINE1 RNA meshwork scaffolds higher-order chromatin organization

Abstract Long interspersed nuclear elements (LINEs) play essential role in shaping chromatin state, while the factors that cooperate with LINEs and their roles in higher-order chromatin organization remain poorly understood. Here we show that MATR3, a nuclear matrix protein, interplays with antisense LINE1 (AS L1) RNAs to form into a gel-like meshwork via phase-separation, providing a partially dynamic platform for chromatin spatial organization. Either depletion of MATR3 or AS L1 RNAs changes nuclear distribution of each other and leads to chromatin reorganization in the nucleus. After MATR3 depletion, topologically associating domains (TADs) that highly transcribed MATR3-associated AS L1 RNAs showed a decrease on local chromatin interactions. Furthermore, amyotrophic lateral sclerosis (ALS)-associated MATR3 mutants alter biophysical features of the MATR3-AS L1 RNA meshwork and cause chromatin reorganization. Collectively, we revealed an essential role of meshwork formed by nuclear matrix and retrotransposon-derived RNAs in gathering chromatin in the nucleus.