Conserved Function of lincRNAs in Vertebrate Embryonic Development Despite Rapid Sequence Evolution

By Igor Ulitsky, Alena Shkumatava, Calvin H. Jan, H. Sive, David P. Bartel. Cell, 2011

1,166 citations recorded by the source corpus.

SUMMARY Thousands of long intervening non-coding RNAs (lincRNAs) have been identified in mammals. To better understand the evolution and functions of these enigmatic RNAs, we used chromatin marks, poly(A)-site mapping and RNA-Seq data, to identify more than 550 distinct lincRNAs in zebrafish. Although these shared many characteristics with mammalian lincRNAs, only 29 had detectable sequence similarity with putative mammalian orthologs, typically restricted to a single short region of high conservation. Other lincRNAs had conserved genomic locations without detectable sequence conservation. Antisense reagents targeting conserved regions of two zebrafish lincRNAs caused developmental defects. Reagents targeting splice sites caused the same defects and were rescued by adding either the mature lincRNA or its human or mouse ortholog. Our study provides a roadmap for identification and analysis of lincRNAs in model organisms and shows that lincRNAs play crucial biological roles during embryonic development with functionality conserved despite limited sequence conservation.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/790a730621508527088abb1515c189ba6f6c4661

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Citations in the corpus

Long Noncoding RNAs: Past, Present, and Future (2013, background): “Some of these have been referred to as “lincRNAs” for “large intergenic (or intervening) noncoding RNAs” (Guttman et al. 2009; Cabili et al. 2011; Ulitsky et al. 2011).”
Long Noncoding RNA MALAT1 Regulates Endothelial Cell Function and Vessel Growth (2014, result): “The function of MALAT1 in the vasculature has not been studied, but the high expression of MALAT1 observed in cultured endothelial cells is consistent with previous results of whole-mount in situ hybridization in zebrafish, which showed a strong staining in the vasculature.(23) The data of the prese”
The rise of regulatory RNA (2014, background): “…of lncRNAs in zebrafish and deletion of sequences specifying lncRNAs in mouse have shown that some confer visible developmental defects 181,191,238,239 , although others do not, including knockouts of the widely expressed Neat1 required for paraspeckle function 240 and some of the most…”
The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse (2013, background): “…gene regulatory networks controlling embryonic stem (ES) cell differentiation (Guttman et al., 2011), and functional studies have provided evidence for the roles of several lncRNAs (Wang et al., 2011; Hu et al., 2011; Kretz et al., 2012; Rinn et al., 2007; Gupta et al., 2010; Ulitsky et al., 2011).”
Braveheart, a long non-coding RNA required for cardiovascular lineage commitment (2013, background): “Though thousands of lncRNAs have been identified across eukaryotes, many are species specific and appear less conserved than protein-coding genes (Cabili et al., 2011; Derrien et al., 2012; Ulitsky et al., 2011).”
Gene regulation by the act of long non-coding RNA transcription (2013, background): “One critical validation step for knockdown studies would be a rescue experiment in which the lncRNA, modified to be invulnerable to the knockdown, is expressed as a transgene under the same transfection conditions [111].”
Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs (2012, background): “This hypothesis would help explain how many lncRNAs with distinct sequences bind the same protein complex (4,34,71); as well as how lncRNAs have functional orthologs that are not conserved at the sequence level (100).”
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Comparative genomics reveals insights into avian genome evolution and adaptation (2014, background): “S20) and it is known to be required for normal embryonic development in zebrafish [Danio rerio] (146).”
Ribosome profiling provides evidence that large non-coding RNAs do not encode proteins (2013, background): “The lincRNAs have recently been shown to play key roles in diverse biological processes and are emerging as an important class of regulatory molecules (Guttman et al., 2011; Guttman and Rinn, 2012; Ørom et al., 2010; Ulitsky et al., 2011; Wang and Chang, 2011).”
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CPAT: Coding-Potential Assessment Tool using an alignment-free logistic regression model (2013, background): “First, most newly discovered transcripts are lncRNAs, which tend to be lineage speciﬁc and less conserved (5,6).”
NONCODEv4: exploring the world of long non-coding RNA genes (2013, background): “Especially, long non-coding RNAs (lncRNAs), which are considered to be >200 nt in length and are often multiexonic (3), have been identified to play critical roles in various processes including embryonic development (4), dosage compensation (5) and immune response (6).”
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