Suppression of progenitor differentiation requires the long noncoding RNA ANCR
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Kun Qu
PROVIDER: E-GEOD-58161 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Suppression of progenitor differentiation requires the long noncoding RNA ANCR.
Kretz Markus M Webster Dan E DE Flockhart Ross J RJ Lee Carolyn S CS Zehnder Ashley A Lopez-Pajares Vanessa V Qu Kun K Zheng Grace X Y GX Chow Jennifer J Kim Grace E GE Rinn John L JL Chang Howard Y HY Siprashvili Zurab Z Khavari Paul A PA
Genes & development 20120202 4
Long noncoding RNAs (lncRNAs) regulate diverse processes, yet a potential role for lncRNAs in maintaining the undifferentiated state in somatic tissue progenitor cells remains uncharacterized. We used transcriptome sequencing and tiling arrays to compare lncRNA expression in epidermal progenitor populations versus differentiating cells. We identified ANCR (anti-differentiation ncRNA) as an 855-base-pair lncRNA down-regulated during differentiation. Depleting ANCR in progenitor-containing populat ...[more]
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Project description:Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized; however, potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7kb lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal differentiation by a post-transcriptional mechanism. TINCR is required for high mRNA abundance of key differentiation genes, many of which are mutated in human skin diseases, including FLG, LOR, ALOXE3, ALOX12B, ABCA12, CASP14 and ELOVL3. TINCR-deficient epidermis lacked terminal differentiation ultrastructure, including keratohyalin granules and intact lamellar bodies. Genome-scale RNA interactome analysis revealed that TINCR interacts with a suite of differentiation mRNAs. TINCR-mRNA interaction occurs through a 25 nucleotide “TINCR box” motif which is strongly enriched in interacting mRNAs \and required for TINCR binding. A high-throughput screen to analyze TINCR binding capacity to ~9,400 human recombinant proteins revealed direct binding of TINCR RNA to the Staufen1 (STAU1) protein. STAU1-deficient tissue recapitulated the impaired differentiation seen with TINCR depletion. Loss of UPF1 and UPF2, both of which are required for STAU1-mediated RNA decay (SMD), however, lacked differentiation impacts. Instead, the TINCR/STAU1 complex seems to mediate stabilization of differentiation mRNAs, such as KRT80. These data identify TINCR as a key lncRNA required for somatic tissue differentiation, which occurs through inducible lncRNA binding to differentiation mRNAs to ensure their expression. Gene expression analysis: To establish a gene expression signature for regenerated human epidermis depleted of TINCR, as well as STAU1, total RNA was isolated in biologic duplicate from organotypic cultures of cells with a non-targeting siRNA, or an siRNA to the gene of interest. This RNA was processed and then hybridized to Affymetrix HG-U133 2.0 Plus arrays.
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Project description:This SuperSeries is composed of the following subset Series: GSE34528: Suppression of Progenitor Differentiation Requires the Long Non-Coding RNA ANCR [HG-U133_Plus_2] GSE34766: Suppression of Progenitor Differentiation Requires the Long Non-Coding RNA ANCR [lincRNA 391k Tiling Array V2] Refer to individual Series
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