N-Methyladenosine on mRNA facilitates a phase-separated nuclear body that suppresses myeloid leukemic differentiation.

N-Methyladenosine (mA) on mRNAs mediates different biological processes and its dysregulation contributes to tumorigenesis. How mA dictates its diverse molecular and cellular effects in leukemias remains unknown. We found that YTHDC1 is the essential mA reader in myeloid leukemia from a genome-wide CRISPR screen and that mA is required for YTHDC1 to undergo liquid-liquid phase separation and form nuclear YTHDC1-mA condensates (nYACs).

The chromatin remodelling factor ATRX suppresses R-loops in transcribed telomeric repeats.

ATRX is a chromatin remodelling factor found at a wide range of tandemly repeated sequences including telomeres (TTAGGG) ATRX mutations are found in nearly all tumours that maintain their telomeres via the alternative lengthening of telomere (ALT) pathway, and ATRX is known to suppress this pathway. Here, we show that recruitment of ATRX to telomeric repeats depends on repeat number, orientation and, critically, on repeat transcription. Importantly, the transcribed telomeric repeats form RNA-DNA hybrids (R-loops) whose abundance correlates with the recruitment of ATRX Here, we show loss of ATRX is also associated with increased R-loop formation.