Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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DICER- andM-BM- AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human stem cell proliferation (RNA-seq)

ABSTRACT: Although liganded nuclear receptors have been established to regulate RNA polymerase II (Pol II)-dependent transcription units, their role in regulating Pol III-transcribed DNA repeats remains largely unknown. Here we report that ~2-3% of the ~100,000-200,000 total human DR2 Alu repeats located in proximity to activated Pol II transcription units are activated by the retinoic acid receptor (RAR) in human embryonic stem cells to generate Pol III-dependent RNAs. These transcripts are processed, initially in aM-BM- DICER-dependent fashion, into small RNAs (~28-65 nt) referred to as repeat-induced RNAs that cause the degradation of a subset of crucial stem-cell mRNAs, includingM-BM- NanogM-BM- mRNA, which modulate exit from the proliferative stem-cell state. This regulation requiresM-BM- AGO3-dependent accumulation of processed DR2 Alu transcripts and the subsequent recruitment ofM-BM- AGO3-associated decapping complexes to the target mRNA. In this way, the RAR-dependent and Pol III-dependent DR2 Alu transcriptional events in stem cells functionally complement the Pol II-dependent neuronal transcriptional program. RNA-sequencing of polyA selected RNA molecules in NTera2/D1 cells and Global Run On (GRO) assay followed by high throughput sequencing (GRO-seq).

ORGANISM(S): Homo sapiens

SUBMITTER: MICHAEL ROSENFELD

PROVIDER: E-GEOD-42563 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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DICER- andM-BM- AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human stem cell proliferation (RNA-seq)

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