Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells

By Sabine Loewer, M. Cabili, M. Guttman, Yuin Han Loh, Kelly Thomas, In-Hyun Park, Manuel Garber, M. Curran, T. Onder, Suneet Agarwal and 6 more. Nature Genetics, 2010

967 citations recorded by the source corpus.

The conversion of lineage-committed cells to induced pluripotent stem cells (iPSCs) by reprogramming is accompanied by a global remodeling of the epigenome, resulting in altered patterns of gene expression. Here we characterize the transcriptional reorganization of large intergenic non-coding RNAs (lincRNAs) that occurs upon derivation of human iPSCs and identify numerous lincRNAs whose expression is linked to pluripotency. Among these, we defined ten lincRNAs whose expression was elevated in iPSCs compared with embryonic stem cells, suggesting that their activation may promote the emergence of iPSCs. Supporting this, our results indicate that these lincRNAs are direct targets of key pluripotency transcription factors. Using loss-of-function and gain-of-function approaches, we found that one such lincRNA (lincRNA-RoR) modulates reprogramming, thus providing a first demonstration for critical functions of lincRNAs in the derivation of pluripotent stem cells.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c8dd2710468c78e464dadbe7b5f7718d422fe186

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Citations in the corpus

Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. (2011, background): “Other studies have inferred and tested the functional role of lincRNAs in processes such as pluripotency and p53 response pathways by associating the expression of lincRNAs with those of protein-coding genes (Guttman et al. 2009; Huarte et al. 2010; Loewer et al. 2010; Hung et al. 2011).”
The functional role of long non-coding RNA in human carcinomas (2011, background): “One such player, the newly discovered long non-coding RNA (lncRNA) genes, demonstrate developmental and tissue specific expression patterns, and aberrant regulation in a variety of diseases, including cancer [18-27].”
A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA (2011, neutral): “…Nagano and Fraser, 2011), such as modulation of apoptosis and invasion (Khaitan et al., 2011), reprogramming of induced pluripotent stem cells (Loewer et al., 2010), marker of cell fate (Ginger et al., 2006) and parental imprinting (Sleutels et al., 2002), indicating that they may represent a…”
Transposable Elements Are Major Contributors to the Origin, Diversification, and Regulation of Vertebrate Long Noncoding RNAs (2013, methodology): “Intriguingly, these instances include two different lncRNAs that are highly expressed in human embryonic stem cells (ESCs) and have been experimentally shown to be implicated in the maintenance of ESC pluripotency: lncRNA-RoR [41] and lncRNA-ES3 [43].”
m6A RNA modification controls cell fate transition in mammalian embryonic stem cells (2014, background): “See also Figure S4A.”
Noncoding RNA:RNA Regulatory Networks in Cancer (2018, background): “Linc-ROR was first identified as a lncRNA that regulates the reprogramming of pluripotent stem cells, which could partly be due to its miRNA sponging effect that regulates stem cell factors OCT4 (POU class 5 homeobox 1), NANOG (Nanog homeobox) and SOX2 (SRY-box 2) [69,70].”
Molecular mechanisms of long noncoding RNAs (2011, background): “…these reprogramming-induced lincRNAs, named lincRNA-RoR, was shown to be directly targeted by the key pluripotency factors Oct4, Sox2, and Nanog through colocalization 906 Molecular Cell 43, September 16, 2011 ª2011 Elsevier Inc. of the three factors close its promoter region (Loewer et al., 2010).”