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Derived and Ancestral RNAs: Comparative Genomics and Evolution of ncRNAs

Final Report Summary - DARCGENS (Derived and Ancestral RNAs: Comparative Genomics and Evolution of ncRNAs)

Prior to the inception of the DARCGENs project little was known concerning the evolution and function of long noncoding RNAs (lncRNAs). Their mystery was heightened by their rapid evolution, their low expression level and their frequent cell-type expression specificity. The DARCGENs project dispelled much of this mystery, showing that (i) their rapid evolution, in general, is a consequence not of Darwinian evolution but of genetic drift and/or neutral evolution; (ii) their functional sequences are very 'patchy' and sparse along transcribed sequence; (iii) that multiexonic lncRNAs often require splicing for their molecular functions; and, (iv) most mammalian lncRNAs are specific to particular lineages, for example, being expressed in mouse but not in rat. Experimental work on several mammalian lncRNAs demonstrated interesting nuclear functions (Dali, Paupar) or cytoplasmic roles (lncSCA7, Cerox1), with lncSCA7 likely being involved in determining the cerebellum and retina-specificity of a disease, spinocerebellar ataxia type 7. The project countered the prevailing view that most lncRNAs act in the nucleus, by showing that several lncRNAs compete with mRNAs for the binding of microRNAs ("competitive endogenous RNAs").

In summary: the DARCGENs project determined the general evolutionary and functional properties of long noncoding RNAs.