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

ABSTRACT: 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE90650 | GEO | 2017/07/26

SECONDARY ACCESSION(S): PRJNA355281

REPOSITORIES: GEO

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High-throughput in vitro DROSHA processing on artificial variants

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Homo sapiens

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

| PRJNA355281 | ENA

Genome-wide quantification of microRNA processing efficiency from RNA-seq data

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2015-03-02 | E-GEOD-58838 | biostudies-arrayexpress

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The bulges control in pri-miRNA processing in the position and strand-dependent manner

Project description:The microRNA (miRNA) biogenesis is responsible for the production of miRNAs that play critical roles in gene expression and numerous human diseases. The adequate biogenesis of miRNAs is largely determined by the efficiency and fidelity of primary microRNA (pri-miRNA) processing by Microprocessor. Here, we investigated the roles of a secondary RNA element, an RNA bulge, in pri-miRNA processing. We discovered that the 3p-strand bulges in positions 7-9 from the Microprocessor cleavage sites (midB_7-9) contributes to determining the cleavage sites of Microprocessor, the 5p- and 3p-strand bugles in positions 10-12 (midB_10-12) blocked the unproductive cleavage, and the 3p-strand bulges in positions 6-7 (seedB) inhibited the productive cleavage of Microprocessor. The 5p-strand midB_10-12 was found enriched and conserved in many pri-miRNAs of humans and other organisms. In addition, by analyzing the published Microprocessor-RNA structure and doing mutagenesis, we identified several amino acid residues of Microprocessor that explains a structure basis for the processing inhibition caused by seedB. The revealed functions of bulges in our study improves our understanding of the pri-miRNA processing by Microprocessor and implies their roles in regulating miRNA expression.

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Microprocessor mediates transcription termination in long noncoding microRNA genes

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Microprocessor depends on hemin to recognize the apical loop of primary microRNA

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2018-03-26 | GSE111431 | GEO

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2015-05-06 | E-GEOD-57363 | biostudies-arrayexpress

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