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Transcriptomic changes in response to modulation of long-non-coding RNA LINC00473

ABSTRACT: Transcriptomic changes in response to modulation of long-non-coding RNA LINC00473

PROVIDER: PRJNA631222 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11734841_1.fastq.gz	Fastqsanger.gz
	SRR11734841_2.fastq.gz	Fastqsanger.gz
	SRR11734842_1.fastq.gz	Fastqsanger.gz
	SRR11734842_2.fastq.gz	Fastqsanger.gz
	SRR11734843_1.fastq.gz	Fastqsanger.gz

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Transcriptomic changes in response to modulation of long-non-coding RNA LINC00473

Project description:Human thermogenic adipose tissue mitigates metabolic disease, raising much interest in understanding its development and function. Here, we show that human thermogenic adipocytes specifically express a primate-specific long non-coding RNA, LINC00473 which is highly correlated with UCP1 expression and decreased in obesity and type-2 diabetes. LINC00473 is detected in progenitor cells, and increases upon differentiation and in response to cAMP. In contrast to other known adipocyte LincRNAs, LINC00473 shuttles out of the nucleus, colocalizes and can be crosslinked to mitochondrial and lipid droplet proteins. Up- or down- regulation of LINC00473 results in reciprocal alterations in lipolysis, respiration and transcription of genes associated with mitochondrial oxidative metabolism. Depletion of PLIN1 results in impaired cAMP-responsive LINC00473 expression and lipolysis, indicating bidirectional interactions between PLIN1, LINC00473 and mitochondrial oxidative functions. Thus, we suggest that LINC00473 is a key regulator of human thermogenic adipocyte function, and reveals a role for a LincRNA in inter-organelle communication and human energy metabolism.

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Project description:Depression is a common disorder that affects women at twice the rate of men. Here we report that long non-coding RNAs (lncRNAs), a recently discovered class of regulatory transcripts, represent about one-third of the differentially expressed genes in the brains of depressed humans, and display complex region- and sex-specific patterns of regulation. We identified the primate-specific, neuronal-enriched gene, linc00473, as downregulated in prefrontal cortex of depressed females but not males. Using viral-mediated gene transfer to express linc00473 in mouse prefrontal cortex neurons, we mirrored the human sex-specific phenotype by inducing stress resilience solely in female mice. This sex-specific phenotype was accompanied by changes in synaptic function and gene expression selectively in female mice and, along with studies of human neuron-like cells in culture, implicates linc00473 as a CREB effector. Together, our studies identify linc00473 as a female-specific driver of stress resilience that is aberrant in female depression.

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