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HASTY modulates miRNA biogenesis by linking pri-miRNA transcription and processing

ABSTRACT: HASTY modulates miRNA biogenesis by linking pri-miRNA transcription and processing

PROVIDER: PRJEB42556 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR5164070_1.fastq.gz	Fastqsanger.gz
	ERR5164070_2.fastq.gz	Fastqsanger.gz
	ERR5160751_1.fastq.gz	Fastqsanger.gz
	ERR5160751_2.fastq.gz	Fastqsanger.gz
	ERR5160632_1.fastq.gz	Fastqsanger.gz

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Project description:To investigate the precise processing mechanism of pri-miRNA, we prepared 38,880 pri-miRNA variants which contain unique barcode sequences (Fang and Bartel, Mol Cell, 60: 131) and performed high-throughput processing experiments.

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The LncRNA NEAT1 Nests RNA Binding Proteins and the Microprocessor to Globally Enhance Pri-miRNA Processing

Project description:MicroRNA biogenesis is known to be modulated by a variety of RNA binding proteins (RBPs), but in most cases, individual RBPs appear to influence the processing of a small number of selective targets. We herein report binding of the NONO/PSF heterodimer to hundreds of expressed pri-miRNAs in HeLa cells to globally enhance pri-miRNA processing by the Drosha/DGCR8 Microprocessor. As NONO/PSF are key components of paraspeckles organized by the lncRNA NEAT1, we find that NEAT1 also has profound effects on global pri-miRNA processing. Mechanistic dissection reveals that NEAT1 broadly interacts with NONO/PSF as well as many other RBPs, and that multiple RNA segments in NEAT1, including a “pseudo pri-miRNA” near its 3’ end, help attract the Microprocessor. These findings suggest a bird nest model for a large lncRNA to orchestrate efficient processing of an entire class of small RNAs in the nucleus.we used small RNA-seq to identify miRNA level in response to secific knockdowns relative to siGFP treatment control

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XPO5 is required for miRNA biogenesis and promotes primary miRNA processing independent of RanGTP

Project description:XPO5 mediates nuclear export of miRNA hairpin precursors in a RanGTP-dependent manner. However, the requirement of XPO5 for global miRNA biogenesis and mammalian development and XPO5-associated RNA species are not determined. Here we show that XPO5 is required for mouse embryonic development and morphogenesis of skin and brain. Loss of XPO5 compromises the biogenesis of most miRNAs and that leads to severe developmental defects. Surprisingly, XPO5 not only associates with miRNA hairpin precursors but also pervasively binds to double-stranded RNA (dsRNA) regions found in many cellular RNAs and some clustered pri-miRNAs. The binding of XPO5 to miR-17~92 pri-miRNAs is RanGTP-independent. Pre-incubation with XPO5 enhances the processing efficiency of the DROSHA/DGCR8 microprocessor. Together, our studies demonstrate the requirement of XPO5 for miRNA biogenesis and mouse development, reveal an unexpected role of XPO5 for recognizing and facilitating the nuclear cleavage of clustered pri-miRNAs and identify numerous cellular RNAs as novel XPO5 subtracts.

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