Chromatin architect of muscle expression (Charme) is a muscle-restricted long noncoding RNA (lncRNA) that plays an important role in myogenesis. Earlier evidence indicates that the nuclear Charme isoform, named pCharme, acts on the chromatin by assisting the formation of chromatin domains where myogenic transcription occurs. By combining RNA antisense purification (RAP) with mass spectrometry and loss-of-function analyses, we have now identified the proteins that assist these chromatin activities. These proteins-which include a sub-set of splicing regulators, principally PTBP1 and the multifunctional RNA/DNA binding protein MATR3-bind to sequences located within the alternatively spliced intron-1 to form nuclear aggregates. Consistent with the functional importance of pCharme interactome in vivo, a targeted deletion of the intron-1 by a CRISPR-Cas9 approach in mouse causes the release of pCharme from the chromatin and results in cardiac defects similar to what was observed upon knockout of the full-length transcript.

Center for Life Nano Istituto Italiano di Tecnologia Viale Regina Elena 291 00161 Rome Italy

Czech Centre of Phenogenomics and Laboratory of Transgenic Models of Diseases Institute of Molecular Genetics of the Czech Academy of Sciences v v i Prumyslova 595 252 50 Vestec Czech Republic

Department of Biochemical Sciences A Rossi Fanelli Sapienza University of Rome P le A Moro 5 00185 Rome Italy

Department of Biology and Biotechnology Charles Darwin Sapienza University of Rome P le A Moro 5 00185 Rome Italy

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