Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution

SummaryThousands of long intervening noncoding RNAs (lincRNAs) have been identified in mammals. To better understand the evolution and functions of these enigmatic RNAs, we used chromatin marks, poly(A)-site mapping and RNA-Seq data to identify more than 550 distinct lincRNAs in zebrafish. Although these shared many characteristics with mammalian lincRNAs, only 29 had detectable sequence similarity with putative mammalian orthologs, typically restricted to a single short region of high conservation. Other lincRNAs had conserved genomic locations without detectable sequence conservation. Antisense reagents targeting conserved regions of two zebrafish lincRNAs caused developmental defects. Reagents targeting splice sites caused the same defects and were rescued by adding either the mature lincRNA or its human or mouse ortholog. Our study provides a roadmap for identification and analysis of lincRNAs in model organisms and shows that lincRNAs play crucial biological roles during embryonic development with functionality conserved despite limited sequence conservation.

Graphical AbstractFigure optionsDownload high-quality image (209 K)Download as PowerPoint slideHighlights
► The zebrafish genome encodes hundreds of long intervening noncoding RNAs (lincRNAs)
► Only 29 of 567 lincRNAs have detectable sequence homology with mammalian lincRNAs
► Two lincRNAs, cyrano and megamind, are required for proper embryonic development
► The functionality of these two lincRNAs is retained in their human/mouse orthologs