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The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

ABSTRACT: The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

PROVIDER: PRJNA804230 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17918667.fastq.gz	Fastqsanger.gz
	SRR17918668.fastq.gz	Fastqsanger.gz
	SRR17918669.fastq.gz	Fastqsanger.gz
	SRR17918670.fastq.gz	Fastqsanger.gz
	SRR17918671.fastq.gz	Fastqsanger.gz

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The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

Project description:Dicer ribonucleases, which generate small RNAs for the RNA interference (RNAi) and microRNA (miRNA) pathways, often have an N-terminal DExD helicase subdomain (also called HEL1). In the mammalian Dicer, HEL1 inhibits RNAi while it appears unnecessary for miRNA biogenesis. To determine its functional significance, we genetically eliminated HEL1 from Dicer in mice. We observed embryonic growth retardation, defects in the cardiopulmonary system, and perinatal lethality. HEL1 suppresses biogenesis of mirtrons, a non-canonical low-abundant class of miRNAs, and is required for high-fidelity cleavage and strand selection during biogenesis of canonical miRNAs. The HEL1 domain itself is essential rather than its helicase activity, because mutations of critical catalytic amino acids do not affect mouse viability or fertility and have minimal impact on miRNA biogenesis. Therefore, HEL1 is a critical structural component of the mammalian Dicer, supporting its role of a conserved structural “mold” that ensures high-fidelity processing and adaptive evolution of mammalian miRNA precursors.

2022-11-03 | GSE196305 | GEO

The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

2022-11-03 | GSE196310 | GEO

The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

2022-11-03 | GSE196309 | GEO

The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

2022-11-03 | GSE196308 | GEO

The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

2022-11-03 | GSE196306 | GEO

The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

Project description:The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

| PRJNA804232 | ENA

The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

Project description:The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

| PRJNA804237 | ENA

The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

Project description:The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

| PRJNA804231 | ENA

The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

Project description:The helicase domain of Dicer ensures essential accuracy of miRNA biogenesis in mice

| PRJNA804233 | ENA

The helicase domain of Dicer ensures strict processing of evolutionarily optimized microRNAs

Project description:Ribonuclease Dicer generates small RNAs for RNA interference (RNAi) and microRNA (miRNA) pathways. Mammalian Dicer produces miRNAs but its tripartite N-terminal helicase domain inhibits processing of double-stranded RNA for RNAi. Mouse oocytes express Dicer, which enhances RNAi because it lacks the helicase’s proximal subdomain HEL1. Here we show that genetic removal of HEL1 in mice causes embryonic growth retardation, defects in the cardiopulmonary system, and perinatal lethality. HEL1 suppresses biogenesis of mirtrons, a non-canonical low-abundant class of miRNAs, and is required for high-fidelity cleavage and strand selection during biogenesis of canonical miRNAs. Essential is the HEL1 structure, not its helicase activity, because mutations of critical aminoacids do not affect viability or fertility and have minimal impact on miRNA biogenesis. Altogether, HEL1 is a critical structural component of Dicer in its role of a highly conserved structural “mold” that ensures high-fidelity processing and adaptive evolution of mammalian miRNA precursors.

2024-04-10 | GSE243016 | GEO

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