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Kerin T, Ramanathan A, Rivas K, Grepo N, Coetzee GA, Campbell DB. A noncoding RNA antisense to moesin at 5p14.1 in autism. Sci Transl Med. 2012 Apr 4 ; 4(128):128ra40. Pubmed Abstract

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Primary Papers: A noncoding RNA antisense to moesin at 5p14.1 in autism.

Comment by:  Karoly Mirnics, SRF Advisor
Submitted 12 April 2012
Posted 12 April 2012

Well done! In addition to DNA sequence diversity, methylation, transcriptional and translational regulation of gene expression, miRNA silencing, alternative splicing, phosphorylation, and trafficking, now we have to think about gene function regulation by antisense RNA pseudogenes, which are very common in the human genome. The Campbell group builds a compelling case that this is a powerful, active, and disease-associated mechanism in autism (and possibly other brain disorders), showing that the moesin pseudogene 1 (MSNP1AS) transcript acts as an endogenous silencer of the moesin gene (MSN). The study builds on GWAS data (SNP rs4307059, associated with autism spectrum diagnosis), identifies a transcript of interest (MSNP1AS), shows disease-context (individuals who carry the ASD-associated rs4307059 T allele showed increased expression of MSNP1AS), report high overexpression in postmortem cerebral cortex of individuals with ASD, and proves functionality (MSNP1AS noncoding RNA binds to MSN, and could regulate levels of moesin protein in human cell lines).

The implications of this study are considerable, and reach well beyond autism research. Our postmortem gene expression profiling efforts during the last decade have routinely encountered elevated or repressed pseudogene transcripts that were associated with various brain disorders. Yet, assuming that they were non-functional transcripts, we largely ignored them, and pseudogenes were almost never a focus of follow-up experiments. This manuscript implies that we should take a good look at the transcriptome data accumulated over the last decade, investigate the possible consequences of altered levels of pseudogene transcripts using bioinformatics, and follow the recipe provided by Campbell and colleagues to assess their functionality.

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