The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse

By P. Grote, L. Wittler, David A. Hendrix, Frederic Koch, Sandra Währisch, Arica Beisaw, Karol Macura, Gaby Bläß, Manolis Kellis, Martin Werber and 1 more. Developmental Cell, 2013

946 citations recorded by the source corpus.

SUMMARY The histone modifying complexes PRC2 and TrxG/MLL play pivotal roles in determining the activation state of genes controlling pluripotency, lineage commitment, and cell differentiation. Long non-coding RNAs (lncRNAs) can bind to either complex, and some have been shown to act as modulators of PRC2 or TrxG/MLL activity. Here we show that the lateral mesoderm-specific lncRNA Fendrr is essential for proper heart and body wall development in the mouse. Embryos lacking Fendrr displayed upregulation of several transcription factors controlling lateral plate or cardiac mesoderm differentiation, accompanied by a drastic reduction in PRC2 occupancy along with decreased H3K27 trimethylation and/or an increase in H3K4 trimethylation at their promoters. Fendrr binds to both the PRC2 and TrxG/MLL complexes, suggesting that it acts as modulator of chromatin signatures that define gene activity. Thus, our work identifies a lncRNA that plays an essential role in fine-tuning the regulatory networks which control the fate of lateral mesoderm derivatives.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d9925b990a59a1755e8aef388fe93f8fe5e349ea

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Citations in the corpus

Transposable Elements Are Major Contributors to the Origin, Diversification, and Regulation of Vertebrate Long Noncoding RNAs (2013, background): “In mouse, Fendrr lincRNA, which has a very restricted pattern of expression in lateral mesoderm [80], initiates within a MTEa (ERVL-MaLR) and 4 different TEs account for 808 nt (33.”
Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches. (2016, background): “Since Fendrr can bind to epigenetic modifying complexes including both PRC2 and TrxG/MLL, it was suggested that the function of Fendrr could be to modulate the activity of such complexes to promote proper development of lateral mesoderm (91).”
Long Noncoding RNAs in Cardiovascular Diseases (2015, neutral): “In this study, the authors used a different knockout strategy (replacement of the target lncRNA with a LacZ reporter cassette) than the one by Grote et al.(86) In their Fendrr mice, although the expression of LacZ gene was not observed in the heart of embryos (at E14.”
lincRNAs: Genomics, Evolution, and Mechanisms (2013, neutral): “…(Tsai et al., 2010), and the polycomb complexes PRC1 (Schoeftner et al., 2006) and PRC2 (Rinn et al., 2007; Zhao et al., 2008; Tsai et al., 2010; Grote et al., 2013; Klattenhoff et al., 2013), although the extent to which some of these interactions are direct and specific remains controversial…”
Long non-coding RNAs and complex diseases: from experimental results to computational models (2016, background): “Recent studies have found several lncRNAs associated with HF (such as Fendrr [84], Trpm3 and Scarb2 [144]) and revealed the critical functions of these lncRNAs in heart development and HF.”
Mechanisms of long noncoding RNA function in development and disease (2016, background): “Fendrr Divergent lncRNA Foxf1 Nucleus Histone modification Development [47, 123]”
How do lncRNAs regulate transcription? (2017, background): “For instance, the Fendrr lncRNA is specifically expressed in the nascent lateral mesoderm in a developing embryo and has been reported to interact with bothMLL and PRC2 complexes (82).”
Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer (2016, background): “These guide lncRNAs are essential for the proper localization of RNPs [26].”
LncRNA2Target v2.0: a comprehensive database for target genes of lncRNAs in human and mouse (2018, methodology): “Recent years, some binding experiments such as immunoprecipitation assays, RNA pull-down assays and luciferase reporter assays was used to identify target genes of lncRNAs (29,30).”
Multiple knockout mouse models reveal lincRNAs are required for life and brain development (2013, methodology): “In accordance with Fendrr having a previously described role in lateral plate mesoderm (Grote et al., 2013), our results suggest a more general role”
Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution (2015, background): “Lastly, lincMKLN1 (type II; also known as PINT [63]), lincFOXF1 (also known as FENDRR [64]), and GAS5 (type II and VI) RNA were all present as nuclear foci in some cell types.”
The multidimensional mechanisms of long noncoding RNA function (2017, background): “Fendrr Differentiation of tissues derived from lateral mesoderm [34]”