Paraspeckles are subnuclear structures formed around NEAT1/MENε/β long noncoding RNA (lncRNA). Here a team led by researchers at Hokkaido University, Japan show that paraspeckles became dramatically enlarged following proteasome inhibition. This enlargement was mainly caused by NEAT1 transcriptional up-regulation, rather than an accumulation of un-degraded paraspeckle proteins. Interestingly, however, using immuno-electron microscopy we found that key paraspeckle proteins become effectively depleted from the nucleoplasm by 50% when paraspeckle assembly is enhanced, suggesting a sequestration mechanism. The team also performed microarrays from NEAT1 knockdown cells and found that NEAT1 represses transcription of several genes including the RNA-specific adenosine deaminase B2 (ADARB2) gene. In contrast, they found that the NEAT1-binding paraspeckle protein SFPQ is required for ADARB2 transcription. This led them to hypothesize that ADARB2 expression is controlled by NEAT1-dependent sequestration of SFPQ. Accordingly, they found ADARB2 expression strongly reduced upon enhanced SFPQ sequestration by proteasome inhibition, with a concomitant reduction in SFPQ-binding to the ADARB2 promoter. Finally, NEAT1-/- fibroblasts were more sensitive to proteasome inhibition that triggered cell death, suggesting that paraspeckles/NEAT1 attenuates the cell death pathway. These data further confirm that paraspeckles are stress-responsive nuclear bodies and provide a model whereby induced NEAT1 controls target gene transcription by protein sequestration into paraspeckles.
- Hirose T, Virnicchi G, Tanigawa A, Naganuma T, Li R, Kimura H, Yokoi T, Nakagawa S, Bénard M, Fox AH, Pierron G. (2013) NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies. Mol Biol Cell [Epub ahead of print]. [abstract]