How are NEAT1 and paraspeckles regulated and how respond to signals within cells?

On September 24th, the international academic journal Nature Cell Biology published the latest research results of the Chen Lingling Research Group of the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, "Genome-wide screening of NEAT1 regulators cross-regulation paraspeckles and mitochondria" (DOI: 10.1038/s41556-018-0204-2).
work reveals important physiological activities such as the communication and interaction between the cytonucleostructure small body paraspeckles and the organar mitochondria involved in regulating apoptosis.
Paraspeckles is a substructure dummy found widely in mammalian cell nuclei, assembled from long non-coding RNA NEAT1 and more than 40 proteins, of which NEAT1 is the skeleton of paraspeckles, which determines whether it can be formed. Early
studies have shown that the expression of NEAT1 and processing and the formation of paraspeckles are affected during processes such as virus invasion, protease inhibition, and neurodegenerative diseases, but how NEAT1 and paraspeckles are regulated and how they respond to signals in cells are unclear.
Figure A: Paraspeckles undergo morphological changes in response to mitochondrial damage.
B:NEAT1 responds to signals from mitochondrial damage by enhancing the retention of paraspeckles on mito-mRNAs to adjust the corresponding physiological processes of mitochondria by feedback.
to study how NEAT1 itself is regulated, the researchers used editing gene technology to insert the EGFP reporting gene at the starting point of NEAT1 transcription, thus creating a cell line neat1G-HeLa that can visualize THE activity of NEAT1 initiators in live cell endogenous sources.
through the genome-wide RNAi screening and analysis of NEAT1G-HeLa, found that some of the genes encoded in the nucleus are significantly rich in mitochondrial function.
interestingly, knocking out these mitochondrial-related proteins makes the spherical paraspeckles, which normally tend to form long strips, which exhibit a more "solidified" state, resulting in a stronger mRNA nuclear retention capacity, including mRNAs (mito-mRNAs) encoded in the nucleus with the regulation of mitochondrial function.
these studies show that these unexpected changes in paraspeckles morphology and function have led to increased nuclear retention in mito-mRNAs, which in turn affects the expression of these mRNAs in response to mitochondrial damage in response.
study also found that in the event of abnormal patterns or quantities of NEAT1 and paraspeckles, the morphology of mitochondria, oxygen consumption rate, ATP synthesis, etc. are affected, and mitochondrial dysfunction eventually affects the rate of cell proliferation.
the formation of a large number of paraspeckles during the apoptosis of the mitochondrial pathway caused by arsenate (SA) and restricttheir expression through mRNAs of the nucleus-trapped cytochrome C, thereby alleviating the apoptosis caused by cytochrome C release.
these results show that NEAT1 regulates the corresponding physiological processes of mitochondria by enhancing the retention of paraspeckles to mito-mRNAs in response to signals from mitochondrial damage.
Chen Lingling's research team has been engaged in long-term non-coding RNA and its functional research.
in the field of NEAT1 research, it is revealed that paraspeckles regulate gene expression by retaining mRNAs containing special para-components (e.g. IRAlus) (Chen et al, 2008 EMBO J); The absence, which in turn affects the expression of nuclear retention genes, and ultimately regulates the normal physiological function of stem cells (Chen and Carmichael, 2009 Mol Cell);
in this latest STUDY of NEAT1, Chen Lingling's research team further revealed the close relationship between the cell nucleus substructure paraspeckles and cytoplasmic mitochondria, showing that under stress conditions, cells regulate the important physiological functions of mitochondrial stability through paraspeckles, and provide a new way to understand the regulation and function of NEAT1, as well as the interaction between intracellular substructures.
under the guidance of researcher Chen Lingling, the work was completed by Wang Yang, ph.d. student of the Institute of Biochemistry and Cells (now a postdoctoral student at Stanford University) and Wang Menan, a ph.d'ites at the Institute of Computational Biology of the Shanghai Institute of Life Sciences of the Chinese Academy of Sciences, and received strong support from Yang Li, a researcher at the Institute of Computational Biology.
the research was supported by funds from the National Fund Committee, the Ministry of Science and Technology, the Chinese Academy of Sciences and the HHMI Foundation, and was supported by the Molecular Biology Technology Platform of the Institute of Biochemistry and Cell Science and the Cell Structure Analysis Technology Platform of the Institute of Plant Physiology and Ecology of the Chinese Academy of Sciences.
Nature Cell Biology magazine also published an opinion piece by Archa Fox, University of Western Australia, entitled A mitochondria-paraspeckle crosstalk, which spoke highly of the work.
Source: Shanghai Institute of Life Sciences.