A direct molecular link between the autism candidate gene RORa and the schizophrenia candidate MIR137.
Retinoic acid-related orphan receptor alpha gene (RORa) and the microRNA MIR137 have both recently been identified as novel candidate genes for neuropsychiatric disorders. RORa encodes a ligand-dependent orphan nuclear receptor that acts as a transcriptional regulator and miR-137 is a brain enriched small non-coding RNA that interacts with gene transcripts to control protein levels. Given the mounting evidence for RORa in autism spectrum disorders (ASD) and MIR137 in schizophrenia and ASD, we investigated if there was a functional biological relationship between these two genes. Herein, we demonstrate that miR-137 targets the 3'UTR of RORa in a site specific manner. We also provide further support for MIR137 as an autism candidate by showing that a large number of previously implicated autism genes are also putatively targeted by miR-137. This work supports the role of MIR137 as an ASD candidate and demonstrates a direct biological link between these previously unrelated autism candidate genes.
Language and Genetics Department, Max Planck Institute for Psycholinguistics, Wundtlaan 1, 6525 XD, Nijmegen, The Netherlands.
Paolo
P
Devanna
1] Language and Genetics Department, Max Planck Institute for Psycholinguistics, Wundtlaan 1, 6525 XD, Nijmegen, The Netherlands [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University, 6525 EN, Nijmegen, The Netherlands.
Sonja C
SC
Vernes
D020413:3' Untranslated Regions / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002460:Cell Line; D002531:Cerebellum / Q000378:metabolism; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics*; D017397:Prefrontal Cortex / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; D015816:Cell Adhesion Molecules, Neuronal; C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; C093438:neuroligin 1; D020813:Receptor, trkB