Transcripts with in silico predicted RNA structure are enriched everywhere in the mouse brain.
BACKGROUND
Post-transcriptional control of gene expression is mostly conducted by specific elements in untranslated regions (UTRs) of mRNAs, in collaboration with specific binding proteins and RNAs. In several well characterized cases, these RNA elements are known to form stable secondary structures. RNA secondary structures also may have major functional implications for long noncoding RNAs (lncRNAs). Recent transcriptional data has indicated the importance of lncRNAs in brain development and function. However, no methodical efforts to investigate this have been undertaken. Here, we aim to systematically analyze the potential for RNA structure in brain-expressed transcripts.


RESULTS
By comprehensive spatial expression analysis of the adult mouse in situ hybridization data of the Allen Mouse Brain Atlas, we show that transcripts (coding as well as non-coding) associated with in silico predicted structured probes are highly and significantly enriched in almost all analyzed brain regions. Functional implications of these RNA structures and their role in the brain are discussed in detail along with specific examples. We observe that mRNAs with a structure prediction in their UTRs are enriched for binding, transport and localization gene ontology categories. In addition, after manual examination we observe agreement between RNA binding protein interaction sites near the 3' UTR structures and correlated expression patterns.


CONCLUSIONS
Our results show a potential use for RNA structures in expressed coding as well as noncoding transcripts in the adult mouse brain, and describe the role of structured RNAs in the context of intracellular signaling pathways and regulatory networks. Based on this data we hypothesize that RNA structure is widely involved in transcriptional and translational regulatory mechanisms in the brain and ultimately plays a role in brain function.
Center for non-coding RNA in Technology and Health, University of Copenhagen, Denmark.
Stefan E
SE
Seemann
Susan M
SM
Sunkin
Michael J
MJ
Hawrylycz
Walter L
WL
Ruzzo
Jan
J
Gorodkin
D000716:Anatomy, Artistic; D000818:Animals; D001271:Atlases as Topic; D001921:Brain / Q000378:metabolism*; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics; D014644:Genetic Variation; D017403:In Situ Hybridization; D051379:Mice; D058977:Molecular Sequence Annotation; D009690:Nucleic Acid Conformation; D011485:Protein Binding / Q000235:genetics; D012313:RNA / Q000737:chemistry* / Q000235:genetics*; D015347:RNA Probes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics; D020506:Untranslated Regions / Q000235:genetics
D015347:RNA Probes; D012333:RNA, Messenger; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D020506:Untranslated Regions; D012313:RNA