Satellite RNAs: Emerging Players in Subnuclear Architecture and Gene Regulation

Satellite DNA is characterized by long, tandemly repeated sequences mainly found in centromeres and pericentromeric chromosomal regions. The recent advent of telomere-to-telomere sequencing data revealed the complete sequences of satellite regions, including centromeric α-satellites and pericentromeric HSat1-3, which together comprise ~ 5.7% of the human genome. Despite possessing constitutive heterochromatin features, these regions are transcribed to produce long noncoding RNAs with highly repetitive sequences that associate with specific sets of proteins to play various regulatory roles. In certain stress or pathological conditions, satellite RNAs are induced to assemble mesoscopic membraneless organelles. Specifically, under heat stress, nuclear stress bodies (nSBs) are scaffolded by HSat3 lncRNAs, which sequester hundreds of RNA-binding proteins. Upon removal of the stressor, nSBs recruit additional regulatory proteins, including protein kinases and RNA methylases, which modify the previously sequestered nSB components. The sequential recruitment of substrates and enzymes enables nSBs to efficiently regulate the splicing of hundreds of pre-mRNAs under limited temperature conditions. This review discusses the structural features and regulatory roles of satellite RNAs in intracellular architecture and gene regulation.