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Frontiers in Plant Science 2018MicroRNAs are small molecules (∼21 nucleotides long) that are key regulators of gene expression. They originate from long stem-loop RNAs as a product of cleavage by a... (Review)
Review
MicroRNAs are small molecules (∼21 nucleotides long) that are key regulators of gene expression. They originate from long stem-loop RNAs as a product of cleavage by a protein complex called Microprocessor. The core components of the plant Microprocessor are the RNase type III enzyme Dicer-Like 1 (DCL1), the zinc finger protein Serrate (SE), and the double-stranded RNA binding protein Hyponastic Leaves 1 (HYL1). Microprocessor assembly and its processing of microRNA precursors have been reported to occur in discrete nuclear bodies called Dicing bodies. The accessibility of and modifications to Microprocessor components affect microRNA levels and may have dramatic consequences in plant development. Currently, numerous lines of evidence indicate that plant Microprocessor activity is tightly regulated. The cellular localization of HYL1 is dependent on a specific KETCH1 importin, and the E3 ubiquitin ligase COP1 indirectly protects HYL1 from degradation in a light-dependent manner. Furthermore, proper localization of HYL1 in Dicing bodies is regulated by MOS2. On the other hand, the Dicing body localization of DCL1 is regulated by NOT2b, which also interacts with SE in the nucleus. Post-translational modifications are substantial factors that contribute to protein functional diversity and provide a fine-tuning system for the regulation of protein activity. The phosphorylation status of HYL1 is crucial for its activity/stability and is a result of the interplay between kinases (MPK3 and SnRK2) and phosphatases (CPL1 and PP4). Additionally, MPK3 and SnRK2 are known to phosphorylate SE. Several other proteins (e.g., TGH, CDF2, SIC, and RCF3) that interact with Microprocessor have been found to influence its RNA-binding and processing activities. In this minireview, recent findings on the various modes of Microprocessor activity regulation are discussed.
PubMed: 29922322
DOI: 10.3389/fpls.2018.00753 -
Proceedings of the National Academy of... Sep 2023MicroRNAs (miRNAs) play an important role in gene regulation. In , mature miRNAs are processed from primary miRNA transcripts by the Dicing complex that contains...
MicroRNAs (miRNAs) play an important role in gene regulation. In , mature miRNAs are processed from primary miRNA transcripts by the Dicing complex that contains Dicer-like 1 (DCL1), SERRATE (SE), and Hyponastic Leaves 1 (HYL1). The Dicing complex can form nuclear dicing bodies (D-bodies) through SE phase separation. Here, we report that Cyclophilin71 (CYP71), a peptidyl-prolyl isomerase (PPIase), positively regulates miRNA processing. We show that CYP71 directly interacts with SE and enhances its phase separation, thereby promoting the formation of D-body and increasing the activity of the Dicing complex. We further show that the PPIase activity is important for the function of CYP71 in miRNA production. Our findings reveal orchestration of miRNA processing by a cyclophilin protein and suggest the involvement of peptidyl-prolyl isomerization, a structural mechanism, in SE phase separation and miRNA processing.
Topics: Arabidopsis; Cyclophilins; MicroRNAs; Plant Leaves; RNA-Binding Proteins; Arabidopsis Proteins
PubMed: 37639607
DOI: 10.1073/pnas.2305244120 -
Nature Communications Jun 2022The formation of membraneless organelles can be a proteotoxic stress control mechanism that locally condenses a set of components capable of mediating protein...
The formation of membraneless organelles can be a proteotoxic stress control mechanism that locally condenses a set of components capable of mediating protein degradation decisions. The breadth of mechanisms by which cells respond to stressors and form specific functional types of membraneless organelles, is incompletely understood. We found that Bcl2-associated athanogene 2 (BAG2) marks a distinct phase-separated membraneless organelle, triggered by several forms of stress, particularly hyper-osmotic stress. Distinct from well-known condensates such as stress granules and processing bodies, BAG2-containing granules lack RNA, lack ubiquitin and promote client degradation in a ubiquitin-independent manner via the 20S proteasome. These organelles protect the viability of cells from stress and can traffic to the client protein, in the case of Tau protein, on the microtubule. Components of these ubiquitin-independent degradation organelles include the chaperone HSP-70 and the 20S proteasome activated by members of the PA28 (PMSE) family. BAG2 condensates did not co-localize with LAMP-1 or p62/SQSTM1. When the proteasome is inhibited, BAG2 condensates and the autophagy markers traffic to an aggresome-like structure.
Topics: Autophagy; Humans; Molecular Chaperones; Proteasome Endopeptidase Complex; Proteolysis; Ubiquitin
PubMed: 35654899
DOI: 10.1038/s41467-022-30751-4 -
Current Genetics Feb 2020The eukaryotic cell is subdivided into distinct functional domains by the presence of both membrane-bound and membraneless organelles. The latter include cytoplasmic... (Review)
Review
The eukaryotic cell is subdivided into distinct functional domains by the presence of both membrane-bound and membraneless organelles. The latter include cytoplasmic granules, like the Processing-body (P-body), that are induced in response to stress and contain specific sets of mRNAs and proteins. Although P-bodies have been evolutionarily conserved, we do not yet understand the full extent of their biological functions in the cell. Early studies suggested that these structures might be sites of mRNA decay as the first protein constituents identified were enzymes involved in mRNA processing. However, more recent work indicates that this is not likely to be the primary function of these granules and has even suggested that P-bodies are sites of long-term mRNA storage. Interestingly, P-bodies and other ribonucleoprotein granules have been found to also contain a variety of signaling molecules, including protein kinases and phosphatases key to the normal control of cell growth and survival. Therefore, P-bodies could have a role in the modulation of cell signaling during particular types of stress. This review discusses both the general implications of such a proposal and one particular example that illustrates how the granule recruitment of a protein kinase can impact overall cell physiology.
Topics: Cytoplasmic Granules; Eukaryotic Cells; Gene Expression Regulation; Organelles; RNA Processing, Post-Transcriptional; RNA Stability; RNA, Messenger; Signal Transduction; Vault Ribonucleoprotein Particles
PubMed: 31317215
DOI: 10.1007/s00294-019-01016-3 -
RNA Biology Jun 2017Cajal bodies (CBs) are distinct sub-nuclear structures that are present in eukaryotic living cells and are often associated with the nucleolus. CBs play important roles... (Review)
Review
Cajal bodies (CBs) are distinct sub-nuclear structures that are present in eukaryotic living cells and are often associated with the nucleolus. CBs play important roles in RNA metabolism and formation of RNPs involved in transcription, splicing, ribosome biogenesis, and telomere maintenance. Besides these primary roles, CBs appear to be involved in additional functions that may not be directly related to RNA metabolism and RNP biogenesis. In this review, we assess possible roles of plant CBs in RNA regulatory pathways such as nonsense-mediated mRNA decay and RNA silencing. We also summarize recent progress and discuss new non-canonical functions of plant CBs in responses to stress and disease. It is hypothesized that CBs can regulate these responses via their interaction with poly(ADP ribose)polymerase (PARP), which is known to play an important role in various physiological processes including responses to biotic and abiotic stresses. It is suggested that CBs and their components modify PARP activities and functions.
Topics: Coiled Bodies; Gene Expression Regulation, Plant; Host-Pathogen Interactions; Nuclear Proteins; Plant Diseases; Plant Physiological Phenomena; Poly(ADP-ribose) Polymerases; RNA Processing, Post-Transcriptional; RNA, Small Nuclear; Ribonucleoproteins, Small Nuclear; Stress, Physiological
PubMed: 27726481
DOI: 10.1080/15476286.2016.1243650 -
Plants (Basel, Switzerland) Feb 2022Based on prior knowledge and with the support of new methodology, solid progress in the understanding of seed life has taken place over the few last years. This update... (Review)
Review
Based on prior knowledge and with the support of new methodology, solid progress in the understanding of seed life has taken place over the few last years. This update reflects recent advances in three key traits of seed life (i.e., preharvest sprouting, genomic imprinting, and stored-mRNA). The first breakthrough refers to cloning of the mitogen-activated protein kinase-kinase 3 (MKK3) gene in barley and wheat. MKK3, in cooperation with ABA signaling, controls seed dormancy. This advance has been determinant in producing improved varieties that are resistant to preharvest sprouting. The second advance concerns to uniparental gene expression (i.e., imprinting). Genomic imprinting primarily occurs in the endosperm. Although great advances have taken place in the last decade, there is still a long way to go to complete the puzzle regarding the role of genomic imprinting in seed development. This trait is probably one of the most important epigenetic facets of developing endosperm. An example of imprinting regulation is polycomb repressive complex 2 (PRC2). The mechanism of PRC2 recruitment to target endosperm with specific genes is, at present, robustly studied. Further progress in the knowledge of recruitment of PRC2 epigenetic machinery is considered in this review. The third breakthrough referred to in this update involves stored mRNA. The role of the population of this mRNA in germination is far from known. Its relations to seed aging, processing bodies (P bodies), and RNA binding proteins (RBPs), and how the stored mRNA is targeted to monosomes, are aspects considered here. Perhaps this third trait is the one that will require greater experimental dedication in the future. In order to make progress, herein are included some questions that are needed to be answered.
PubMed: 35214823
DOI: 10.3390/plants11040490 -
Acta Biochimica Polonica 2016During reaction to stress caused by viral infection, RNA granules are formed in order to protect mRNA. Stress granules (SG) and processing bodies (PB) provide cell... (Review)
Review
During reaction to stress caused by viral infection, RNA granules are formed in order to protect mRNA. Stress granules (SG) and processing bodies (PB) provide cell homeostasis and mRNA stability. They are formed, for example, during polio virus and MRV (mammalian orthoreovirus) infections. Some viruses, such as influenza virus and HTLV-1 (Human T-lymphotropic virus 1), block the formation of granules. In addition, there are viruses like West Nile Virus, Hepatitis C Virus (HCV) or human Herpes viruses, which influence the functioning of the granules.
Topics: Animals; Cytoplasmic Granules; Flaviviridae; Homeostasis; Host-Pathogen Interactions; Humans; Picornaviridae; Protein Biosynthesis; Reoviridae; Retroviridae; Virus Diseases
PubMed: 26894234
DOI: 10.18388/abp.2015_1060 -
Nature Communications Jul 2022Insulin is a potent inducer of mRNA transcription and translation, contributing to metabolic regulation. Insulin has also been suggested to regulate mRNA stability...
Insulin is a potent inducer of mRNA transcription and translation, contributing to metabolic regulation. Insulin has also been suggested to regulate mRNA stability through the processing body (P-body) molecular machinery. However, whether and how insulin regulates mRNA stability via P-bodies is not clear. Here we show that the E3-ligase TRIM24 is a critical factor linking insulin signalling to P-bodies. Upon insulin stimulation, protein kinase B (PKB, also known as Akt) phosphorylates TRIM24 and stimulates its shuttling from the nucleus into the cytoplasm. TRIM24 interacts with several critical components of P-bodies in the cytoplasm, promoting their polyubiquitylation, which consequently stabilises Pparγ mRNA. Inactivation of TRIM24 E3-ligase activity or prevention of its phosphorylation via knockin mutations in mice promotes hepatic Pparγ degradation via P-bodies. Consequently, both knockin mutations alleviate hepatosteatosis in mice fed on a high-fat diet. Our results demonstrate the critical role of TRIM24 in linking insulin signalling to P-bodies and have therapeutic implications for the treatment of hepatosteatosis.
Topics: Animals; Insulin; Mice; Nuclear Proteins; PPAR gamma; Processing Bodies; RNA, Messenger; Transcription Factors; Ubiquitin-Protein Ligases
PubMed: 35803934
DOI: 10.1038/s41467-022-31735-0 -
Frontiers in Microbiology 2021RNA granules are cytoplasmic, non-membranous ribonucleoprotein compartments that form ubiquitously and are often referred to as foci for post-transcriptional gene... (Review)
Review
RNA granules are cytoplasmic, non-membranous ribonucleoprotein compartments that form ubiquitously and are often referred to as foci for post-transcriptional gene regulation. Recent research on RNA processing bodies (PB) and stress granules (SG) has shown wide implications of these cytoplasmic RNA granules and their components in suppression of RNA translation as host intracellular innate immunity against infecting viruses. Many RNA viruses either counteract or co-opt these RNA granules; however, many fundamental questions about DNA viruses with respect to their interaction with these two RNA granules remain elusive. Kaposi's sarcoma-associated herpesvirus (KSHV), a tumor-causing DNA virus, exhibits two distinct phases of infection and encodes ∼90 viral gene products during the lytic phase of infection compared to only a few (∼5) during the latent phase. Thus, productive KSHV infection relies heavily on the host cell translational machinery, which often links to the formation of PB and SG. One major question is how KSHV counteracts the hostile environment of RNA granules for its productive infection. Recent studies demonstrated that KSHV copes with the translational suppression by cellular RNA granules, PB and SG, by expressing ORF57, a viral RNA-binding protein, during KSHV lytic infection. ORF57 interacts with Ago2 and GW182, two major components of PB, and prevents the scaffolding activity of GW182 at the initial stage of PB formation in the infected cells. ORF57 also interacts with protein kinase R (PKR) and PKR-activating protein (PACT) to block PKR dimerization and kinase activation, and thus inhibits eIF2α phosphorylation and SG formation. The homologous immediate-early regulatory protein ICP27 of herpes simplex virus type 1 (HSV-1), but not the EB2 protein of Epstein-Barr virus (EBV), shares this conserved inhibitory function with KSHV ORF57 on PB and SG. Through KSHV ORF57 studies, we have learned much about how a DNA virus in the infected cells is equipped to evade host antiviral immunity for its replication and productive infection. KSHV ORF57 would be an excellent viral target for development of anti-KSHV-specific therapy.
PubMed: 35069491
DOI: 10.3389/fmicb.2021.794431 -
Neuroscience Insights 2022Separated face- and body-responsive brain networks have been identified that show strong responses when observers view faces and bodies. It has been proposed that face...
Separated face- and body-responsive brain networks have been identified that show strong responses when observers view faces and bodies. It has been proposed that face and body processing may be initially separated in the lateral occipitotemporal cortex and then combined into a whole person representation in the anterior temporal cortex, or elsewhere in the brain. However, in contrast to this proposal, our recent study identified a common coding of face and body orientation (ie, facing direction) in the lateral occipitotemporal cortex, demonstrating an integration of face and body information at an early stage of face and body processing. These results, in combination with findings that show integration of face and body identity in the lateral occipitotemporal, parahippocampal and superior parietal cortex, and face and body emotional expression in the posterior superior temporal sulcus and medial prefrontal cortex, suggest that face and body integration may be more distributed than previously considered. I propose a new model of face and body integration, where areas at the intersection of face- and body-responsive regions play a role in integrating specific properties of faces and bodies, and distributed regions across the brain contribute to high-level, abstract integration of shared face and body properties.
PubMed: 35991808
DOI: 10.1177/26331055221119221