Paraspeckles are phase-separated nuclear bodies in the interchromatin space of mammalian nuclei that are built on two isoforms of the long non-coding RNA NEAT1. More than 40 RNA-binding proteins associate with NEAT1 in a core-shell arrangement. Paraspeckle components serve as multipurpose molecular scaffolds and are involved in various RNA metabolic processes, such as transcriptional regulation, RNA processing, or RNA editing.
NEAT1 serves as a bait for RNA interference factors to promote efficient miRNA biogenesis in unperturbed cells. Replication stress induces the expression of NEAT1 by the tumour suppressor p53, while loss of NEAT1 hyper-sensitises cells to DNA damage. Intriguingly, NEAT1 and other components of paraspeckles are deregulated in cancer and linked to the DNA damage response.
However, the molecular mechanisms that integrate the nuclear RNA metabolism, paraspeckle biology and genome maintenance are poorly understood. We combine basic molecular cell biology and biochemistry with transcriptomics and tumour models to understand the role of paraspeckle components for genome stability and cellular transformation. We aim to decipher the dynamics of paraspeckle composition and discover novel mechanisms that link paraspeckles to genome stability and cellular transformation. We aim to decipher the dynamics of paraspeckle composition and discover novel mechanisms that link paraspeckles to genome stability and tumorigenesis.