Abstract
Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) reported to be frequently deregulated in various types of cancers and neurodegenerative processes. NEAT1 is an indispensable structural component of paraspeckles (PSs), which are dynamic and membraneless nuclear bodies that affect different cellular functions, including stress response. Furthermore, increasing evidence supports the crucial role of NEAT1 and essential structural proteins of PSs (PSPs) in the regulation of the DNA damage repair (DDR) system. This review aims to provide an overview of the current knowledge on the involvement of NEAT1 and PSPs in DDR, which might strengthen the rationale underlying future NEAT1-based therapeutic options in tumor and neurodegenerative diseases.
Highlights
Nuclear paraspeckle assembly transcript 1 (NEAT1) is a functionally conserved long non-coding RNA, abundantly expressed in a variety of mammalian cell types
In human breast cancer cells, Adriaens et al showed that treatment with the p53-inducer Nutlin-3 induces NEAT1 expression levels in association with an increase in PSs formation; at the same time, they found that NEAT1 silencing leads to accumulation of DNA damage and to induction of DNA damage repair (DDR) signaling, as confirmed by the enhancement in γH2AX (Histone H2AX) levels and DNA damage foci formation, as well as the increase in the phosphorylated fraction of KAP1 (KRAB-associated Protein 1), known to be an ATM substrate [3]
Focusing on the homologous recombination (HR) pathway, we found a reduction of both RAD51 (DNA repair protein RAD51 homolog 1) protein expression level and the phosphorylated fraction of kinase proteins CHK1 and CHK2, all of them involved in the DNA damage checkpoint
Summary
Nuclear paraspeckle assembly transcript 1 (NEAT1) is a functionally conserved long non-coding RNA (lncRNA), abundantly expressed in a variety of mammalian cell types. NEAT1 overexpression, together with an increase in PSs density, has been found in ALS motor neurons, suggesting a direct contribution of NEAT1 in ALS disease by modulating the functions of ALS-associated. The findings from different studies raise the possibility that defects in the DDR underlie brain aging and the development of age-related neurodegenerative disorders [12]. These considerations prompt further investigation on the NEAT1 and PSs roles in DDR in neurodegenerative diseases. We provide an overview of the current knowledge on NEAT1 and PS proteins (PSPs) dynamics, which could be instrumental for a better comprehension of disease pathobiology and for the design of novel NEAT1-based therapeutic options in human diseases
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.