Transcriptomic analyses from across eukaryotes indicate that most of the genome is transcribed at some point in the developmental trajectory of an organism. One class of these transcripts is termed long intergenic noncoding RNAs (lincRNAs). Recently, attention has focused on understanding the evolutionary dynamics of lincRNAs, particularly their conservation within genomes. Here, we take a comparative genomic and phylogenetic approach to uncover factors influencing lincRNA emergence and persistence in the plant family Brassicaceae, to which Arabidopsis thaliana belongs. We searched 10 genomes across the family for evidence of >5000 lincRNA loci from A. thaliana. From loci conserved in the genomes of multiple species, we built alignments and inferred phylogeny. We then used gene tree/species tree reconciliation to examine the duplication history and timing of emergence of these loci. Emergence of lincRNA loci appears to be linked to local duplication events, but, surprisingly, not whole genome duplication events (WGD), or transposable elements. Interestingly, WGD events are associated with the loss of loci for species having undergone relatively recent polyploidy. Lastly, we identify 1180 loci of the 6480 previously annotated A. thaliana lincRNAs (18%) with elevated levels of conservation. These conserved lincRNAs show higher expression, and are enriched for stress-responsiveness and cis-regulatory motifs known as conserved noncoding sequences (CNSs). These data highlight potential functional pathways and suggest that CNSs may regulate neighboring genes at both the genomic and transcriptomic level. In sum, we provide insight into processes that may influence lincRNA diversification by providing an evolutionary context for previously annotated lincRNAs.

MicroRNAs (miRNAs) are an abundant and diverse class of small, non-protein coding RNAs that guide the post-transcriptional repression of messenger RNA (mRNA) targets in a sequence-specific manner. Hundreds, if not thousands of distinct miRNA sequences have been described, each of which has the potential to regulate a large number of mRNAs. Over the last decade, miRNAs have been ascribed roles in nearly all biological processes in which they have been tested. More recently, interest has grown in understanding how individual miRNAs evolved, and how they are regulated. In this work, we demonstrate that Transposable Elements are a source for novel miRNA genes and miRNA target sites. We find that primate-specific miRNA binding sites were gained through the transposition of Alu elements. We also find that remnants of Mammalian Interspersed Repeat transposition, which occurred early in mammalian evolution, provide highly conserved functional miRNA binding sites in the human genome. We also provide data to support that long non-coding RNAs (lncRNAs) can provide a novel miRNA binding substrate which, rather than inhibiting the miRNA target, inhibits the miRNA. As such, lncRNAs are proposed to function as endogenous miRNA "sponges," competing for miRNA binding and reducing miRNA-mediated repression of protein-coding mRNA targets. We also explored how dynamic changes to miRNA binding sites can occur by A-to-I editing of the 3 `UTRs of mRNA targets. These works, together with knowledge gained from the regulatory activity of endogenous and exogenously added miRNAs, provided a platform for algorithm development that can be used in the rational design of artificial RNAi triggers with improved target specificity. The cumulative results from our studies identify and in some cases clarify important mechanisms for the emergence of miRNAs and miRNA binding sites on large (over eons) and small (developmental) time scales, and help in translating these gene silencing processes into practical application.

Since its early discovery as a messenger, RNA has been shown to play a diverse set of regulatory, structural and even catalytic roles. The more recent understanding that the genome is pervasively transcribed stimulated the discovery of a new prevalent class of long non coding RNAs (lncRNAs). While these are lower abundant and relatively less conserved than other class of functional RNAs, lncRNAs are emerging as key players in different cellular processes in development and disease.

This project concerns an exploration of the presence and interactions of long non-coding RNA transcripts in an experimental atherosclerosis mouse model with relevance for human abdominal aortic aneurysm development. 187 long noncoding RNAs, two of them entirely novel, were found to be differentially expressed between angiotensin II treated (developing abdominal aortic aneurysms) and non-treated apolipoprotein E deficient mice (not developing aneurysms) harvested after the same period of time. These transcripts were also studied with regards to co-expression network connections. Eleven previously annotated and two novel long non-coding RNAs were present in two significantly disease correlated co-expression groups that were further profiled with respect to network properties, Gene Ontology terms and MetaCore© connections.

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