Understanding the role of divergent lncRNA-TF pairs in regulating embryonic cell-fate decisions
Final Report Abstract
In humans, protein-coding genes are often accompanied by bidirectionally transcribed, divergent non-coding RNAs. However, the relevance of this phenomenon remains poorly understood. Using an hESC-based cardiac differentiation model, we define a class of divergent lncRNAs, yin yang lncRNAs (yylncRNA), that mirror the cell-type specific expression pattern of their protein-coding counterparts. yylncRNAs are preferentially encoded from the genomic loci of key developmental cell-fate regulators. Most yylncRNAs are spliced, polyadenylated transcripts showing comparable expression patterns in vivo in mouse and in human embryos. Signifying their developmental function, the key mesoderm-specifier BRACHYURY (T) is accompanied by YYLNCT, which localizes to the active T locus during mesoderm commitment. Mechanistically, YYLNCT binds the de novo DNA methyltransferase DNMT3B, inhibiting its activity at the T locus during mesoderm differentiation. Consistent with a transcriptspecific function, depletion of YYLNCT disrupts the activation of the T locus, thereby abolishing mesoderm commitment. Collectively, we report a lncRNA-mediated regulatory layer safeguarding embryonic cell-fate transitions.
Publications
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Detection of RNA–DNA binding sites in long noncoding RNAs. Nucleic Acids Research, 47(6), e32-e32.
Kuo, Chao-Chung; Hänzelmann, Sonja; Sentürk, Cetin Nevcin; Frank, Stefan; Zajzon, Barna; Derks, Jens-Peter; Akhade, Vijay Suresh; Ahuja, Gaurav; Kanduri, Chandrasekhar; Grummt, Ingrid; Kurian, Leo & Costa, Ivan G.
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Loss of genomic integrity induced by lysosphingolipid imbalance drives ageing in the heart. EMBO reports, 20(4).
Ahuja, Gaurav; Bartsch, Deniz; Yao, Wenjie; Geissen, Simon; Frank, Stefan; Aguirre, Aitor; Russ, Nicole; Messling, Jan‐Erik; Dodzian, Joanna; Lagerborg, Kim A.; Vargas, Natalia Emilse; Muck, Joscha Sergej; Brodesser, Susanne; Baldus, Stephan; Sachinidis, Agapios; Hescheler, Juergen; Dieterich, Christoph; Trifunovic, Aleksandra; Papantonis, Argyris ... & Kurian, Leo
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yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs. Cell Stem Cell, 24(2), 318-327.e8.
Frank, Stefan; Ahuja, Gaurav; Bartsch, Deniz; Russ, Nicole; Yao, Wenjie; Kuo, Joseph Chao-Chung; Derks, Jens-Peter; Akhade, Vijay Suresh; Kargapolova, Yulia; Georgomanolis, Theodore; Messling, Jan-Erik; Gramm, Marie; Brant, Lilija; Rehimi, Rizwan; Vargas, Natalia Emilse; Kuroczik, Alina; Yang, Tsun-Po; Sahito, Raja Ghazanfar Ali; Franzen, Julia ... & Kurian, Leo
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Long non-coding RNA LASSIE regulates shear stress sensing and endothelial barrier function. Communications Biology, 3(1).
Stanicek, Laura; Lozano-Vidal, Noelia; Bink, Diewertje Ilse; Hooglugt, Aukie; Yao, Wenjie; Wittig, Ilka; van Rijssel, Jos; van Buul, Jaap Diederik; van Bergen, Anke; Klems, Alina; Ramms, Anne Sophie; Le Noble, Ferdinand; Hofmann, Patrick; Szulcek, Robert; Wang, ShengPeng; Offermanns, Stefan; Ercanoglu, Meryem Seda; Kwon, Hyouk-Bum; Stainier, Didier ... & Boon, Reinier Abraham
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A specialized mRNA translation circuit instated in pluripotency presets the competence for cardiogenesis in humans.
Bartsch, Deniz; Kalamkar, Kaustubh; Ahuja, Gaurav; Lackmann, Jan-Wilm; Bazzi, Hisham; Clamer, Massimiliano; Mendjan, Sasha; Papantonis, Argyris & Kurian, Leo
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circRAB3IP modulates cell proliferation by reorganizing gene expression and mRNA processing in a paracrine manner. RNA, 28(11), 1481-1495.
Josipovic, Natasa; Ebbesen, Karoline K.; Zirkel, Anne; Danieli-Mackay, Adi; Dieterich, Christoph; Kurian, Leo; Hansen, Thomas B. & Papantonis, Argyris
