DNA methylation directs microRNA biogenesis
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ABSTRACT:
PROVIDER: PRJNA514058 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:MicroRNA (miRNA) biogenesis initiates co-transcriptionally, but how the Microprocessor machinery pinpoints the locations of short precursor miRNA sequences within long flanking regions of the transcript is not known. Here we show that miRNA biogenesis depends on DNA methylation. We found that miRNAs whose corresponding coding sequence’s flanking regions are highly methylated are expressed more, have greater sequence conservation, and are more likely to drive cancer-related phenotypes than miRNAs encoded by unmethylated loci. Accordingly, the removal of DNA methylation from miRNAs leads to their downregulation. Further, we found that MeCP2 binding to the DNA of methylated miRNAs halts RNA polymerase II elongation, an inactivation that leads to enhanced processing of primary miRNA by Drosha. Taken together, our data reveal that DNA methylation directly affects miRNA biogenesis.
2019-01-10 | GSE124879 | GEO
Project description:MicroRNA (miRNA) biogenesis initiates co-transcriptionally, but how the Microprocessor machinery pinpoints the locations of short precursor miRNA sequences within long flanking regions of the transcript is not known. Here we show that miRNA biogenesis depends on DNA methylation. When the regions flanking the miRNA coding sequence are highly methylated, the miRNAs are more highly expressed, have greater sequence conservation, and are more likely to drive cancer-related phenotypes than miRNAs encoded by unmethylated loci. We show that the removal of DNA methylation from miRNA loci leads to their downregulation. Further, we found that MeCP2 binding to methylated miRNA loci halts RNA polymerase II elongation, leading to enhanced processing of the primary miRNA by Drosha. Taken together, our data reveal that DNA methylation directly affects miRNA biogenesis.
| S-EPMC6906426 | biostudies-literature
Project description:MicroRNA (miRNA) biogenesis is a tightly controlled multi-step process operated in the nucleus by the activity of the Large Drosha Complex (LDC). Through high resolution mass spectrometry (MS) analysis we discovered that the LDC is extensively methylated, with 82 distinct methylated sites associated to 16 out of 23 subunits of the LDC. The majority of these modifications occurs on arginine (R)- residues (61), leading to 86 methylation events, while 29 lysine (K)-methylation events occurs on 21 sites of the complex. Interestingly, the depletion and pharmacological inhibition of PRMT1 lead to a widespread alteration of the methylation state of the complex and induce global decrease of miRNA expression, as a consequence of the specific impairment of the pri-to-pre-miRNA processing step. In particular, we show that the reduced methylation of the ILF3 subunit of the complex is linked to its diminished binding to the target pri-miRNAs. Overall, our study uncovers a previously uncharacterized role of R-methylation in the regulation of the LDC activity in mammalian cells, thus effecting global miRNA levels.
2019-10-23 | PXD011617 | Pride
Project description:Noncoding RNA-mediated DNA methylation directs nucleosome positioning
| PRJNA623375 | ENA
Project description:We explored the mechanism by which RdDM affects nucleosome positioning in Arabidopsis thaliana. We showed that POLV has a direct effect on nucleosomes through the SWI/SNF complex. We found that the AGO4-siRNA complex is involved in nucleosome positioning via IDN2. Moreover, the SWI/SNF complex is not required for DNA methylation in positioned nucleosomes. Instead, we found that DNA methylation is needed for nucleosome positioning in differentially methylated regions. Taken together, we propose a model where the RdDM pathway directs nucleosome positioning through DNA methylation to establish transcriptional gene silencing.
2023-04-06 | GSE148173 | GEO
Project description:In mammals, the acquisition of the germline from the soma provides the germline with an essential challenge, the necessity to erase and reset genomic methylation. In the male germline RNA-directed DNA methylation silences young active transposable elements (TEs). The PIWI protein MIWI2 (PIWIL4) and its associated PIWI-interacting RNAs (piRNAs) are proposed to tether MIWI2 to nascent TE transcripts and instruct DNA methylation. The mechanism by which MIWI2 directs de novo TE methylation is poorly understood but central to the immortality of the germline. Here, we define the interactome of MIWI2 in foetal gonocytes that are undergoing de novo genome methylation and identify a novel MIWI2-associated factor, SPOCD1, that is essential for young TE methylation and silencing. The loss of Spocd1 in mice results in male specific infertility and does not impact on piRNA biogenesis nor localization of MIWI2 to the nucleus. SPOCD1 is a nuclear protein and its expression is restricted to the period of de novo genome methylation. We found SPOCD1 co-purified in vivo with DNMT3L and DNMT3A, components of the de novo methylation machinery as well as constituents of the NURD and BAF chromatin remodelling complexes. We propose a model whereby tethering of MIWI2 to a nascent TE transcript recruits repressive chromatin remodelling activities and the de novo methylation apparatus through its association with SPOCD1. In summary, we have identified a novel and essential executor of mammalian piRNA-directed DNA methylation.
2020-06-22 | PXD016701 | Pride
Project description:Interventions: Gold Standard:colonoscopy and pathology;Index test:Stool multi-target DNA and microRNA-135b
Primary outcome(s): Stool multi-target DNA and microRNA-135b
Study Design: Diagnostic test for accuracy
| 2681097 | ecrin-mdr-crc
Project description:PRMT1 regulates microRNA biogenesis through the methylation of the Large Drosha Complex
| PRJNA562522 | ENA
Project description:In plants, the known microRNAs (miRNAs) are produced as ~21 nucleotide (nt) duplexes from their precursors by Dicer like 1 (DCL1). They are incorporated into Argonaute 1 (AGO1) protein to regulate target gene expression primarily through mRNA cleavage. We report here the discovery of a new class of miRNAs in the model monocot rice (Oryza sativa). These are 24 nt in length and require another member of the Dicer family, DCL3, for their biogenesis. The 24 nt long miRNAs (lmiRNAs) are loaded into AGO4 clade proteins according to hierarchical rules, depending on the upstream biogenesis machinery and the 5’ terminal nucleotide. We demonstrated that lmiRNAs direct DNA methylation at loci from which they are produced as well as in trans at their target genes and play roles in gene regulation. Considered together, our findings define a novel miRNA pathway that mediates DNA methylation. Small RNAs were prepared from Rice total extract in wide type, dcl1, dcl3, rdr2 dbsRNA mutant and AGO4a, AGO4b, and AGO16 complexes, ligated to a 3' adaptor and a 5' acceptor sequentially, and then RT-PCR amplified. PCR products were reamplified using a pair of solexa cloning primers and then provided for sequencing. For technical details, see Wu, L., Zhang, Q., Zhou, H., Ni, F., Wu, X., and Qi, Y. (2009). Rice microRNA effector complexes and targets. The Plant Cell, 21: 3421-3435.
2010-03-12 | E-GEOD-20748 | biostudies-arrayexpress
Project description:In developing male germ cells, prospermatogonia, two Piwi proteins, MILI and MIWI2, use piRNA guides to repress transposable element (TE) expression and ensure genome stability and proper gametogenesis. In addition to their roles in post-transcriptional TE repression, both proteins are required for DNA methylation of TE sequences. Here we analyzed the effect of Miwi2 deficiency on piRNA biogenesis and transposon repression. Miwi2-deficiency had only a minor impact on piRNA biogenesis; however, the piRNA profile of Miwi2-knockout mice indicated overexpression of several LINE1 TE families that led to activation of the ping-pong piRNA cycle. Furthermore, we found that MILI and MIWI2 have distinct functions in TE repression in the nucleus. MILI is responsible for DNA methylation of a larger subset of TE families than MIWI2 suggesting that the proteins have independent roles in establishing DNA methylation patterns. Small RNA profiles (19-30 nt range) of embryonic (E16.5) and post-natal (P10) testis of Miwi2 mutant mice and matched heterozygote controls. mRNA profiles of embryonic testis (E16.5) of heterozygote control mice and of postnatal testis (P10) of Miwi2 and Mili mutants and heterozygote controls. CpG methylation BS-seq profile of postnatal (P10) spermatocytes of Miwi2 mutant mice and matched heterozygote controls.
2015-07-11 | E-GEOD-70731 | biostudies-arrayexpress