HomeENGLISH MAGAZINENeed for a NEAT memory? Non-coding "junk" seeks for epigenetic FOStery

Need for a NEAT memory? Non-coding “junk” seeks for epigenetic FOStery

Researchers at the University of Alabama at Birmingham have found that a tissue-specific, non-coding RNA called NEAT1 has a major, previously unrecognized role in memory formation. It’s have been long known that DNA contains the code that gives cells the genetic information they need to build and maintain an organism. Adenine (A), Thymine (T), Guanine (G) and Cytosine (C) are the four letters of this code. RNA is the messenger that transmits the code to individual cells in the form of proteins. In RNAs, the letter T is substituted with Uracyl (U). In transfer RNAs (needed for protein synthesis), there are also modified bases whose function is poorly understood, let them alone code for other still unknown instructions. However, there are also non-coding RNAs (lncRNA), which do carry instructions to a cell without coding for proteins and whose role has been poorly understood. The lncRNA transcripts are partially similar to messenger RNAs (mRNAs) as they are frequently transcribed by RNA polymerase II.  However, recent studies have shown that lncRNAs can regulate gene expression, participate in X-chromosome silencing, genome imprinting, chromatin modification, transcriptional activation and many other important biological processes. Recently, science has come to understand that non-coding RNA may play a more important role than originally believed. These molecules are increasingly becoming even markers for pathological situations, e.g. heart attack, brain stroke or autoimmunity like rheumatoid arthritis.

Farah Lubin, PhD, associate professor in the Department of Neurobiology and primary investigator of the study, explained the underlying mechanisms of the discovery an potential implication as well: “NEAT1 is a tissue-specific, non-coding RNA found in the hippocampus region of the brain. This brain region is most associated with learning and memory. While it has some association with cancer in other parts of the body, we have discovered that, in the hippocampus, NEAT1 appears to regulate memory formation. When NEAT1 is on, or active, we do not learn as well. But when presented with an outside learning experience, it turns off, allowing the brain to learn from the outside stimulus. Using a car analogy, the engine might be running; but when the brakes are on, the car does not move. You have to take off the brakes and hit the gas to get the car to move. NEAT1 is the brake: when it is on, we aren’t learning, at least not as much as we might with it off. In a younger brain, when presented with stimulus that promotes learning, NEAT1 turns off. Since one of the hallmarks of aging is a decline in memory, we wondered if NEAT1 was implicated in that decline. Further research should also examine the potential of using the same CRISPR technology to ultimately prevent NEAT1 overexpression in older humans to help boost memory formation. The goal is to find ways to enhance memory due to aging or conditions with memory deficits, such as Alzheimer’s disease or other dementias”

One of the genes that NEAT1 acts upon is c-Fos, which is a transcription factor necessary for memory formation along with its partner c-Jun, to form the powerful activator AP-1. In an aging brain, NEAT1 is on more than it is in a younger brain, interfering with the epigenetic regulation of c-Fos, which disrupts its memory functions. Using siRNA techniques in a mouse model, scientists were able to turn off NEAT1 in older mice. After that, the mice demonstrated normal abilities in learning and memory. Suppression of the NEAT1 RNA revealed widespread changes in gene transcription as well as perturbations of histone 3 (H3) lysine methylation, a repressive histone modification mark that is dysregulated in the aging hippocampus. NEAT1 mediated a transcriptional repression via histone methylation at the c-Fos promoter, corresponding with observed changes in c-Fos mRNA levels. In addition, down-regulation of lncRNA NEAT1 results in changes in the expression of multiple gene transcripts involved in ion channel function following neuronal activation. The next step was to change the level of NEAT1 in younger mice, using CRISPR gene-editing technology. Boosting the presence of NEAT1 in younger mice caused a decline in their ability to learn and remember. This gives very strong evidence that NEAT1 and its effects on the epigenetic control of c-Fos are one of the keys to memory formation. This sets the stage for more research into the potential roles played by other non-coding RNAs in human health.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Butler AA et al. Lubin FD. Sci Signal. 2019 Jul 2; 12(588).

Chang-Wei W et al. Front. Behav. Neurosci. Sept 2018.

Barry, G. et al., Jonkhout N. Scient Rep. 2017; 7:40127. 

Dott. Gianfrancesco Cormaci
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di due brevetti sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of patents concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica e salute sui siti web salutesicilia.com, medicomunicare.it e in lingua inglese sul sito www.medicomunicare.com
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