PT - JOURNAL ARTICLE AU - Jennifer Y Tan AU - Adriano Biasini AU - Robert S Young AU - Ana C Marques TI - Splicing of enhancer-associated lincRNAs contributes to enhancer activity AID - 10.26508/lsa.202000663 DP - 2020 Apr 01 TA - Life Science Alliance PG - e202000663 VI - 3 IP - 4 4099 - https://www.life-science-alliance.org/content/3/4/e202000663.short 4100 - https://www.life-science-alliance.org/content/3/4/e202000663.full SO - Life Sci. Alliance2020 Apr 01; 3 AB - Transcription is common at active mammalian enhancers sometimes giving rise to stable enhancer-associated long intergenic noncoding RNAs (elincRNAs). Expression of elincRNA is associated with changes in neighboring gene product abundance and local chromosomal topology, suggesting that transcription at these loci contributes to gene expression regulation in cis. Despite the lack of evidence supporting sequence-dependent functions for most elincRNAs, splicing of these transcripts is unexpectedly common. Whether elincRNA splicing is a mere consequence of cognate enhancer activity or if it directly impacts enhancer function remains unresolved. Here, we investigate the association between elincRNA splicing and enhancer activity in mouse embryonic stem cells. We show that multi-exonic elincRNAs are enriched at conserved enhancers, and the efficient processing of elincRNAs is strongly associated with their cognate enhancer activity. This association is supported by their enrichment in enhancer-specific chromatin signatures; elevated binding of co-transcriptional regulators; increased local intra-chromosomal DNA contacts; and strengthened cis-regulation on target gene expression. Our results support the role of efficient RNA processing of enhancer-associated transcripts to cognate enhancer activity.