Impact of the Autism-Associated Long Noncoding RNA MSNP1AS on Neuronal Architecture and Gene Expression in Human Neural Progenitor Cells.
We previously identified the long noncoding RNA (lncRNA)MSNP1AS(moesin pseudogene 1, antisense) as a functional element revealed by genome wide significant association with autism spectrum disorder (ASD).MSNP1ASexpression was increased in the postmortem cerebral cortex of individuals with ASD and particularly in individuals with the ASD-associated genetic markers on chromosome 5p14.1. Here, we mimicked the overexpression ofMSNP1ASobserved in postmortem ASD cerebral cortex in human neural progenitor cell lines to determine the impact on neurite complexity and gene expression. ReNcell CX and SK-N-SH were transfected with an overexpression vector containing full-lengthMSNP1AS. Neuronal complexity was determined by the number and length of neuronal processes. Gene expression was determined by strand-specific RNA sequencing.MSNP1ASoverexpression decreased neurite number and neurite length in both human neural progenitor cell lines. RNA sequencing revealed changes in gene expression in proteins involved in two biological processes: protein synthesis and chromatin remodeling. These data indicate that overexpression of the ASD-associated lncRNAMSNP1ASalters the number and length of neuronal processes. The mechanisms by whichMSNP1ASoverexpression impacts neuronal differentiation may involve protein synthesis and chromatin structure. These same biological processes are also implicated by rare mutations associated with ASD, suggesting convergent mechanisms.
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. jjdewitt@usc.edu.
Jessica J
JJ
DeWitt
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. grepo@usc.edu.
Nicole
N
Grepo
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. brentwil@usc.edu.
Brent
B
Wilkinson
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. evgrafov@med.usc.edu.|Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. evgrafov@med.usc.edu.
Oleg V
OV
Evgrafov
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. knowles@med.usc.edu.|Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. knowles@med.usc.edu.
James A
JA
Knowles
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. dbcampbe@med.usc.edu.|Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. dbcampbe@med.usc.edu.
Daniel B
DB
Campbell
RNA-sequencing; autism; lncRNA; long noncoding RNA; neuronal progenitor; noncoding RNA
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