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Expression profiling of miR-294 and Mbd2 siRNA transfected Dgcr8-/- mESCs by high throughput sequencing

ABSTRACT: RNA-seq analysis on CTR, miR-294, and siMbd2 transfected Dgcr8-/- ESCs showed that Mbd2 is responsible for the change of expression of a significant portion of genes that are regulated by miR-290 cluster

ORGANISM(S): Mus musculus

PROVIDER: GSE64428 | GEO | 2015/12/31

SECONDARY ACCESSION(S): PRJNA270999

REPOSITORIES: GEO

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Expression profiling of miR-294 and Mbd2 siRNA transfected Dgcr8-/- mESCs by high throughput sequencing

Project description:RNA-seq analysis on CTR, miR-294, and siMbd2 transfected Dgcr8-/- ESCs showed that Mbd2 is responsible for the change of expression of a significant portion of genes that are regulated by miR-290 cluster mRNA profiles of CTR, miR-294 and siMbd2 transfected Dgcr8-/- ESCs were generated by deep sequencing, in duplicate, using pair-end Illumina.

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Project description:DiGeorge syndrome critical region 8 (DGCR8) is a critical component of the canonical microprocessor complex for microRNA biogenesis. However, the non-canonical functions of DGCR8 have not been studied. Here, we demonstrate that DGCR8 plays an important role in maintaining heterochromatin organization and attenuating aging. An N-terminal-truncated version of DGCR8 (DR8dex2) accelerated senescence in human mesenchymal stem cells (hMSCs) independent of its miRNA-processing activity, which is mediated by its C-terminal domains. Further studies revealed that DGCR8 maintained heterochromatin organization by interacting with the nuclear envelope protein Lamin B1, and heterochromatin-associated proteins, KAP1 and HP1 Overexpression of any of these proteins, including DGCR8, reversed premature senescent phenotypes in DR8dex2 hMSCs. Finally, DGCR8 was downregulated in pathologically and naturally aged hMSCs, whereas DGCR8 overexpression alleviated hMSC aging and osteoarthritis in mice. Taken together, these analyses uncovered a novel, miRNA processing-independent role for DGCR8 in maintaining heterochromatin organization and attenuating senescence. DGCR8 may therefore represent a new therapeutic target for alleviating human aging-related disorders.

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