Chromatin associated α-satellite RNA maintains chromosome stability by re-establishing SAF-A in the mitotic cell cycle [RNA-seq]

α-satellite RNA has been shown to interact with specific sets of RNA-binding proteins. By forming complexes with centromere proteins CENPA, CENPB, and CENPC, α-satellite RNA demonstrated its essential role in maintaining functional human centromeres. Also, α-satellite RNA has been reported to interact with SUV39H1, which is the histone methyltransferase that is responsible for H3K9me3. Together with the findings in mice and some other eukaryotes that RNA components are required for the recruitment of heterochromatin proteins and the maintenance of pericentric heterochromatin, it has long been suspected that α-satellite RNA might also be involved in the heterochromatin formation and recruitment of HP1 in human cells. In this study, we identified Scaffold Attachment Factor-A (SAF-A) as a novel α-satellite RNA binding protein. SAF-A, also known as hnRNPU, the most abundant member in the hnRNP complex, was initially identified as the major component of the nuclear scaffold. It binds to the nuclear scaffold in AT-rich regions through its DNA-binding domain. In recent years, several studies have suggested that SAF-A may play a more fundamental and general role in nuclear organization in interphase. Depletion of SAF-A will lead to pronounced chromatin condensation of gene-rich regions and global changes in 3D genome architecture.