PML functions as SUMO E3 for microprocessor and modulates global miRNA biogenesis
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ABSTRACT:
PROVIDER: PRJNA874742 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The goal is to test if promyelocytic leukemia protein (PML) enhances miRNA biogenesis at a global level by regulating the microprocessor. Nuclear PML isoforms directly interact with ribonuclease III enzyme Drosha and robustly promote the processing of primary to precursor miRNAs.
2025-08-31 | GSE212276 | GEO
Project description:The budding yeast E3 SUMO ligase Mms21, a component of the Smc5-6 complex, regulates sister chromatid cohesion, DNA replication, and DNA repair. We identify a role for Mms21 in ribosome biogenesis. The mms21RINGD mutant exhibits reduced rRNA production, nuclear accumulation of 60S and 40S ribosomal proteins, and elevated Gcn4 translation. Genes involved in ribosome biogenesis and translation are down-regulated in the mms21RINGD mutant. Examining gene expression profile of mms21RINGD mutant compared to wild-type by RNA Seq using Ilumina sequencing
2015-06-13 | E-GEOD-69826 | biostudies-arrayexpress
Project description:The budding yeast E3 SUMO ligase Mms21, a component of the Smc5-6 complex, regulates sister chromatid cohesion, DNA replication, and DNA repair. We identify a role for Mms21 in ribosome biogenesis. The mms21RINGD mutant exhibits reduced rRNA production, nuclear accumulation of 60S and 40S ribosomal proteins, and elevated Gcn4 translation. Genes involved in ribosome biogenesis and translation are down-regulated in the mms21RINGD mutant.
2015-06-13 | GSE69826 | GEO
Project description:The precise control of miR-17~92 microRNA (miRNA) is essential for normal development and overexpression of certain miRNAs from this cluster is oncogenic. Here we find the relative expression of the six miRNAs processed from the primary (pri-miR-17~92) transcript is dynamically regulated during embryonic stem cell differentiation. We identify a new miRNA biogenesis intermediate, termed ‘progenitor-miRNA’ (pro-miRNA), that is an efficient substrate for Microprocessor. An autoinhibitory 5’ RNA fragment is cleaved to generate pro-miRNA and selectively license Microprocessor-mediated production of pre-miR-17, -18a, -19a, 20a, and -19b. Using genetic, biochemical, and structural methods we define two complementary cis-regulatory repression domains required for the formation of this inhibitory RNA conformation. We find the endonuclease CPSF3 (CPSF73), and the Spliceosome-associated ISY1 are required for pro-miRNA biogenesis and expression of all miRNAs within the cluster except miR-92. Thus, developmentally regulated generation of pro-miRNA explains the posttranscriptional control of miR-17~92 expression in development. Illumina RNAseq in WT, dgcr8-/- and dicer-/- mESCs and small RNA seq in WT mESCs
2015-05-11 | E-GEOD-68699 | biostudies-arrayexpress
Project description:Precise control of miRNA biogenesis is of extreme importance, since mis-regulation of miRNAs underlies or exacerbates many disease states. The Microprocessor complex, composed of DROSHA and DGCR8, carries out the first of two cleavage steps in canonical miRNA biogenesis. Despite recent advances in understanding the molecular mechanism of Microprocessor, the role of N-terminal regions of DROSHA is less characterized due their high intrinsic disorder. Here we demonstrate that Microprocessor forms liquid-liquid phase separated (LLPS) condensates in select tissues in C. elegans. We find that an intrinsically disordered region (IDR) near the N-terminus of DRSH-1/DROSHA is required for normal development and biogenesis of a subset of miRNAs. Despite the known role of IDRs in LLPS, the role of the DRSH-1 IDR in miRNA biogenesis and development is genetically separable from its contribution to granule formation. A cis region of an IDR-dependent miRNA confers IDR-dependence to another miRNA, suggesting that the IDR may recognize sequences or structures in the miRNA transcript. Future studies will further elucidate the specificity of this interaction and the putative role of Microprocessor condensates.
2025-07-20 | GSE289120 | GEO
Project description:Regulation of microRNA (miR) biogenesis is complex and stringently controlled. Here we identify the kinase GSK3B as an important modulator of global miR biogenesis at microprocessor level. Repression of GSK3B activity reduces Drosha activity towards pri-miRs, leading to accumulation of unprocessed pri-miRs and reduction of pre-miRs and mature miRs without altering levels or cellular localisationof miR biogenesisproteins. Conversly, GSK3B activation increases Drosha activityand mature miR accumulation. GSK3B achieves this through promoting Drosha:cofactor and Drosha:pri-miR interactions: it binds to DGCR8 and p72 in the Microprocessor, an effect dependent of RNA. Indeed GSK3B itself can immunoprecipitate pri-miRs, suggesting possible RNA binding capacity. Kinase assays identify the mechanism for GSK3B-enhansed Drosha activity, which requires GSK3B nuclear localisation, as phosphorylation of Drosha at s300 and/or s302 confirmed by enhanced Drosha activity and association with cofactors, and increased abundance of mature microRNAs in the presence of phospho-mimetic Drosha. Functional implicatons of GSK3B-enhanced miR biogenesis are illustrated by increased levels of GSK3B-upregulatd miR targets following GSK3B inhibition. These data, the first link GSK3B with the miR cascade in humans, hilight a novel pro-biogenesis role for GSK3B in increasing miR biogenesis as a component of the Microprocessor complex with wide ranging consiquences.
2016-05-20 | GSE81141 | GEO
Project description:The precise control of miR-17~92 microRNA (miRNA) is essential for normal development and overexpression of certain miRNAs from this cluster is oncogenic. Here we find the relative expression of the six miRNAs processed from the primary (pri-miR-17~92) transcript is dynamically regulated during embryonic stem cell differentiation. We identify a new miRNA biogenesis intermediate, termed ‘progenitor-miRNA’ (pro-miRNA), that is an efficient substrate for Microprocessor. An autoinhibitory 5’ RNA fragment is cleaved to generate pro-miRNA and selectively license Microprocessor-mediated production of pre-miR-17, -18a, -19a, 20a, and -19b. Using genetic, biochemical, and structural methods we define two complementary cis-regulatory repression domains required for the formation of this inhibitory RNA conformation. We find the endonuclease CPSF3 (CPSF73), and the Spliceosome-associated ISY1 are required for pro-miRNA biogenesis and expression of all miRNAs within the cluster except miR-92. Thus, developmentally regulated generation of pro-miRNA explains the posttranscriptional control of miR-17~92 expression in development.
2015-05-11 | GSE68699 | GEO
Project description:Abstract: The Promyelocytic Leukemia protein (PML) and its associated nuclear bodies have re-cently emerged as essential factors for maintaining the characteristics of embryonic stem (ES) cells. However, the full repertoire of PML driven gene regulatory events in ES cells is not resolved. In this report we have studied the role of PML in shaping the proteomic and SUMO proteomic landscape in ES cells. Our analysis of the PML KD proteome revealed a suppression of proteins related with self-renewal and an up-regulation of proteins vital for translation and proteasome functions, reflecting a cellular transition from pluripotency to differentiation. Major targets of PML-directed sumoylation include pluripotency factors, chromatin organizers and cell cycle regulators. We demonstrate that PML promotes the sumoylation of SALL1 and CDCA8, two proteins that are highly expressed in undifferentiated ES cells. SALL1 sumoylation increases the activation of the Wnt pathway, contributing to its ability to inhibit ES cell differentiation. Similarly, CDCA8 sumoylation enhances its capacity to promote cell proliferation. Our results demonstrate that PML maintains ES cell functions by modulating the abundance or sumoylation of key regulators involved in pluripotency and cell cycle progression.
2025-05-07 | PXD058024 | Pride
Project description:MicroRNAs (miRNAs) are short RNAs that post-transcriptionally regulate gene expression. In canonical miRNA biogenesis, primary miRNAs are transcribed from intergenic loci or intronic regions by RNA polymerase II, sequentially cleaved by the Microprocessor complex and Dicer, and resulting mature miRNAs are loaded into Argonaute to repress target mRNAs. A minority of miRNAs are generated via noncanonical biogenesis pathways that bypass the Microprocessor and/or Dicer. Here, we describe a new Pol III-dependent, Microprocessor -independent, and Dicer-dependent biogenesis pathway exemplified by the mir-1829 family in C. elegans. Although the mir-1829 family loci reside in intronic regions of protein-coding genes, we show that the miRNAs are derived from independent Pol III transcripts. Unlike other Pol III-dependent miRNAs, the mir-1829 family small RNAs are the dominant species derived from their loci, rather than fragments of a larger functional noncoding RNA. These germline-enriched miRNAs are loaded in multiple miRNA Argonautes, including the recently-characterized germline Argonaute ALG-5, which we demonstrate is repressive when tethered to a reporter transcript. We extend these findings, identifying additional Pol III-transcribed and noncanonical small RNAs in C. elegans and human datasets, including human miR-4521. These young, noncanonical miRNAs may represent an early snapshot in the evolution of de novo miRNA genes.
2025-06-12 | GSE282009 | GEO
Project description:Roots are very important at different stages of plant growth, and the formation of lateral roots is essential for strengthening the roots and absorbing nutrients from the soil. Therefore, it is of great significance to uncover the molecular mechanism of lateral root development in plants for understanding plant life process and improving plant adaptation to environment. As an important post-translational modification of small protein types, small ubiquitin-like modifier is involved in many biological processes such as transcriptional regulation, cell cycle regulation, and immune response. SUMO E3 ligase plays a key role in the SUMO process and plays an important role in plant growth and development. In Arabidopsis thaliana, SIZ1 encodes a SUMO E3 ligase, which plays an important role in plant life, especially in stress response. We analyzed the expression sites of SIZ1 and found that it was obviously expressed in lateral roots, especially in the nucleus of lateral roots. Previous studies on SIZ1 mainly focused on biological stress and abiotic stress, but the molecular mechanism of SIZ1 regulating lateral roots has not been studied. We propose a mechanism by which hemicylation of LBD29 mediated by SIZ1 regulates the occurrence of lateral roots in Arabidopsis Thaliana, which provides a new idea and direction for subsequent research on lateral root development.
2026-07-22 | GSE271343 | GEO