biostudies-literatureMuch CNIH/NIGMSDeutsche ForschungsgemeinschaftHoward Hughes Medical InstituteHoward Hughes Medical Institute (HHMINational Institutes of HealthNIGMS NIH HHS842-853https://www.ebi.ac.uk/biostudies/studies/S-EPMC9074896biostudies-literatureUnknown28(6)Long noncoding RNAs (lncRNAs) are rapidly evolving and thus typically poorly conserved in their sequences. How these sequence differences affect the characteristics and potential functions of lncRNAs with shared synteny remains unclear. Here we show that the syntenically conserved lncRNA <i>Firre</i> displays distinct expression and localization patterns in human and mouse. Single molecule RNA FISH reveals that in a range of cell lines, mouse <i>Firre</i> (<i>mFirre</i>) is predominantly nuclear, while human <i>FIRRE</i> (<i>hFIRRE</i>) is distributed between the cytoplasm and nucleus. This localization pattern is maintained in human/mouse hybrid cells expressing both human and mouse <i>Firre</i>, implying that the localization of the lncRNA is species autonomous. We find that the majorityRNA (New York, N.Y.)Evolutionary divergence of <i>Firre</i> localization and expression.PMC9074896P01 GM099117K99GM137072K99 GM137072MU 4462/1-1Much CHwang TRinn JLSmallegan MJDumbovic GHanson SDfalseEvolutionary divergence of <i>Firre</i> localization and expression.Long noncoding RNAs (lncRNAs) are rapidly evolving and thus typically poorly conserved in their sequences. How these sequence differences affect the characteristics and potential functions of lncRNAs with shared synteny remains unclear. Here we show that the syntenically conserved lncRNA <i>Firre</i> displays distinct expression and localization patterns in human and mouse. Single molecule RNA FISH reveals that in a range of cell lines, mouse <i>Firre</i> (<i>mFirre</i>) is predominantly nuclear, while human <i>FIRRE</i> (<i>hFIRRE</i>) is distributed between the cytoplasm and nucleus. This localization pattern is maintained in human/mouse hybrid cells expressing both human and mouse <i>Firre</i>, implying that the localization of the lncRNA is species autonomous. We find that the majority2022-01-01T00:00:00Z2022 Jun2025-04-05T11:42:47.693Z2024-12-04T13:32:55.463ZS-EPMC90748963530442110.1261/rna.079070.121