NF90 Modulates Processing of a Subset of Human Pri-miRNAs
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ABSTRACT:
PROVIDER: PRJNA547631 | ENA |
REPOSITORIES: ENA
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Project description:This SuperSeries is composed of the SubSeries listed below. MicroRNAs are predicted to regulate the expression of more than 60% of mammalian genes and play fundamental roles in most biological processes. Deregulation of miRNA expression is a hallmark of most cancers and further investigation of mechanisms controlling miRNA biogenesis is needed. The dsRNA-binding protein, NF90 has been shown to act as a competitor of Microprocessor for a limited number of pri-miRNAs. Here, we show that NF90 has a more widespread effect on pri-miRNA biogenesis than previously thought. Genome-wide approaches revealed that NF90 is associated with the stem region of 38 pri-miRNAs, in a manner that is largely exclusive of Microprocessor. Following loss of NF90, 25 NF90-bound pri-miRNAs showed increased abundance of mature miRNA products. NF90-targeted pri-miRNAs are highly stable, having a lower free energy and fewer mismatches compared to all pri-miRNAs. Mutations leading to less stable structures reduced NF90 binding while increasing pri-miRNA stability led to ac quisition of NF90 association, as determined by RNA EMSA. NF90-bound and modulated pri-miRNAs are embedded in introns of host genes and expression of several is concomitantly modulated, including an oncogene implicated in metastasis of hepatocellular carcinoma, TIAM2. These data suggest that NF90 controls the processing of a subset of highly stable, intronic miRNAs.
2020-05-01 | GSE132341 | GEO
Project description:MicroRNAs (miRNAs) are predicted to regulate the expression of >60% of mammalian genes and play fundamental roles in most biological processes. Deregulation of miRNA expression is a hallmark of most cancers and further investigation of mechanisms controlling miRNA biogenesis is needed. The double stranded RNA-binding protein, NF90 has been shown to act as a competitor of Microprocessor for a limited number of primary miRNAs (pri-miRNAs). Here, we show that NF90 has a more widespread effect on pri-miRNA biogenesis than previously thought. Genome-wide approaches revealed that NF90 is associated with the stem region of 38 pri-miRNAs, in a manner that is largely exclusive of Microprocessor. Following loss of NF90, 22 NF90-bound pri-miRNAs showed increased abundance of mature miRNA products. NF90-targeted pri-miRNAs are highly stable, having a lower free energy and fewer mismatches compared to all pri-miRNAs. Mutations leading to less stable structures reduced NF90 binding while increasing pri-miRNA stability led to acquisition of NF90 association, as determined by RNA electrophoretic mobility shift assay (EMSA). NF90-bound and downregulated pri-miRNAs are embedded in introns of host genes and expression of several host genes is concomitantly reduced. These data suggest that NF90 controls the processing of a subset of highly stable, intronic miRNAs.
| S-EPMC7337520 | biostudies-literature
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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.
2018-12-13 | GSE117600 | GEO
Project description:The in vitro high-throughput human pri-miRNA processing assays were conducted to check whether mismatches and wobble base pairs in the upper stem of pri-miRNAs affects the DROSHA cleavage.
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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.
2021-08-23 | GSE158060 | GEO