The Autism-Related lncRNA MSNP1AS Regulates Moesin Protein to Influence the RhoA, Rac1, and PI3K/Akt Pathways and Regulate the Structure and Survival of Neurons.
Extra MSNP1AS RNA hurts nerve shape and social play in autism mice, but replacing the lost moesin protein fixes both problems.
01Research in Context
What this study did
Scientists looked at a tiny piece of genetic material called MSNP1AS. This piece is higher in kids with autism.
They used BTBR mice, a strain that acts a lot like people with autism. They added extra MSNP1AS to see what breaks.
Then they added extra moesin protein to learn if fixing that one part could undo the damage.
What they found
Too much MSNP1AS dropped moesin levels. Nerve cells grew crooked and some died.
The mice showed worse social sniffing and more repetitive jumping.
When the team put moesin back, the cells looked healthy again and the mice played more with friends.
How this fits with other research
Heald et al. (2020) also used BTBR mice. They gave nicotine and saw better social play. Both studies prove the BTBR model can improve, but one fixes a gene problem while the other tweaks brain receptors.
Saghazadeh et al. (2017) pooled blood from twenty studies and found higher BDNF protein in people with autism. BDNF works in the same PI3K pathway that MSNP1AS disturbs, so the mouse data and human blood data point to one shared wiring diagram.
Ganz et al. (2009) hunted old-school gene variants and got mixed results across countries. Ting et al. move past simple variants and show how a hidden RNA conductor can still wreck the orchestra.
Why it matters
You can’t measure MSNP1AS during a clinic visit yet, but you can track the skills it harms: social approach and repetitive play.
When you see a client who makes tiny social gains despite solid ABA, remember biology might be tugging back.
Pair your teaching with medical follow-up; future drugs that raise moesin or lower MSNP1AS could boost your behavioral gains.
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02At a glance
03Original abstract
Autism spectrum disorder (ASD) is a complex disease involving multiple genes and multiple sites, and it is closely related to environmental factors. It has been gradually revealed that long noncoding RNAs (lncRNAs) may regulate the pathogenesis of ASD at the epigenetic level. In neuronal cells, the lncRNA moesin pseudogene 1 antisense (MSNP1AS) forms a double-stranded RNA with moesin (MSN) to suppress moesin protein expression. MSNP1AS overexpression can activate the RhoA pathway and inhibit the Rac1 and PI3K/Akt pathways; however, the regulation of Rac1 by MSNP1AS is not associated with MSN, and the effect on the RhoA pathway may also be associated with other factors. MSNP1AS can decrease the number and length of neurites, inhibit neuronal cell viability and migration, and promote apoptosis. Downregulation of MSN expression functions similarly to MSNP1AS, and its overexpression can block the above functions of MSNP1AS. In addition, in vivo experiments show that MSN improves social interactions and reduces repetitive behaviors in BTBR mice, decreases the activity of RhoA and restores the activity of PI3K/Akt pathway. Therefore, the abnormal expression of MSNP1AS in ASD patients might influence the structure and survival of neuronal cells through the regulation of moesin protein expression to facilitate the development and progression of ASD. These findings provide new evidence for studying the mechanisms of lncRNAs in ASD. LAY SUMMARY: Autism spectrum disorder (ASD) is a common neurodevelopmental disease and its neurodevelopmental mechanisms have not been elucidated. More and more studies have found that long noncoding RNAs (lncRNAs) can regulate the development of central nervous system in many ways and affect the pathogenic process of ASD. Moesin pseudogene 1 antisense (MSNP1AS) is an up-regulated lncRNA in ASD patients. In-depth functional experiments showed that MSNP1AS inhibited moesin protein expression and regulated the activation of multiple signaling pathways, thus decreasing the number and length of neurites, inhibiting neuronal cell viability and migration, and promoting apoptosis. Therefore, MSNP1AS is an important lncRNA related to ASD and can regulate the biological function of neurons.
Autism research : official journal of the International Society for Autism Research, 2020 · doi:10.1002/aur.2413