PT - JOURNAL ARTICLE AU - Tuck, Alex C AU - Natarajan, Kedar Nath AU - Rice, Greggory M AU - Borawski, Jason AU - Mohn, Fabio AU - Rankova, Aneliya AU - Flemr, Matyas AU - Wenger, Alice AU - Nutiu, Razvan AU - Teichmann, Sarah AU - Bühler, Marc TI - Distinctive features of lincRNA gene expression suggest widespread RNA-independent functions AID - 10.26508/lsa.201800124 DP - 2018 Aug 01 TA - Life Science Alliance PG - e201800124 VI - 1 IP - 4 4099 - https://www.life-science-alliance.org/content/1/4/e201800124.short 4100 - https://www.life-science-alliance.org/content/1/4/e201800124.full SO - Life Sci. Alliance2018 Aug 01; 1 AB - Eukaryotic genomes produce RNAs lacking protein-coding potential, with enigmatic roles. We integrated three approaches to study large intervening noncoding RNA (lincRNA) gene functions. First, we profiled mouse embryonic stem cells and neural precursor cells at single-cell resolution, revealing lincRNAs expressed in specific cell types, cell subpopulations, or cell cycle stages. Second, we assembled a transcriptome-wide atlas of nuclear lincRNA degradation by identifying targets of the exosome cofactor Mtr4. Third, we developed a reversible depletion system to separate the role of a lincRNA gene from that of its RNA. Our approach distinguished lincRNA loci functioning in trans from those modulating local gene expression. Some genes express stable and/or abundant lincRNAs in single cells, but many prematurely terminate transcription and produce lincRNAs rapidly degraded by the nuclear exosome. This suggests that besides RNA-dependent functions, lincRNA loci act as DNA elements or through transcription. Our integrative approach helps distinguish these mechanisms.