-
Molecular Biology of the Cell Jul 2020Cajal bodies (CBs) are subnuclear domains involved in the formation of ribonucleoproteins (RNPs) including small nuclear RNPs (snRNPs). CBs associate with specific gene...
Cajal bodies (CBs) are subnuclear domains involved in the formation of ribonucleoproteins (RNPs) including small nuclear RNPs (snRNPs). CBs associate with specific gene loci, which impacts expression and provides a platform for the biogenesis of the nascent transcripts emanating from these genes. Here we report that CBs can associate with the C19MC microRNA (miRNA) gene cluster, which suggests a role for CBs in the biogenesis of animal miRNAs. The machinery involved in the formation of miRNAs includes the Drosha/DGCR8 complex, which processes primary-miRNA to precursor miRNA. Further processing of precursor miRNA by Dicer and other components generates mature miRNA. To test if CBs influence the expression and formation of miRNAs, we examined two representative miRNAs (miR-520 h and let-7a) in conditions that disrupt CBs. CB disruption correlates with alterations in the level of primary and mature miRNA and the let-7a mRNA target, HMGA2. We have also found that the processing of some small CB-specific RNAs (scaRNAs) is directly mediated by the Drosha/DGCR8 complex. ScaRNAs form scaRNPs, which play an important role in snRNP formation. Collectively, our results demonstrate that CBs and the miRNA processing machinery functionally interact and together contribute to the biogenesis of miRNAs and snRNPs.
Topics: Cell Line, Tumor; Coiled Bodies; DNA-Binding Proteins; HMGA2 Protein; Humans; MicroRNAs; Models, Biological; Multigene Family; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA-Binding Proteins; Ribonuclease III; Substrate Specificity
PubMed: 32432989
DOI: 10.1091/mbc.E20-02-0144 -
RNA Biology Jun 2017Box C/D and box H/ACA snoRNAs are abundant non-coding RNAs that localize in the nucleolus and mostly function as guides for nucleotide modifications. While a large pool... (Review)
Review
Box C/D and box H/ACA snoRNAs are abundant non-coding RNAs that localize in the nucleolus and mostly function as guides for nucleotide modifications. While a large pool of snoRNAs modifies rRNAs, an increasing number of snoRNAs could also potentially target mRNAs. ScaRNAs belong to a family of specific RNAs that localize in Cajal bodies and that are structurally similar to snoRNAs. Most scaRNAs are involved in snRNA modification, while telomerase RNA, which contains H/ACA motifs, functions in telomeric DNA synthesis. In this review, we describe how box C/D and H/ACA snoRNAs are processed and assembled with core proteins to form functional RNP particles. Their biogenesis involve several transport factors that first direct pre-snoRNPs to Cajal bodies, where some processing steps are believed to take place, and then to nucleoli. Assembly of core proteins involves the HSP90/R2TP chaperone-cochaperone system for both box C/D and H/ACA RNAs, but also several factors specific for each family. These assembly factors chaperone unassembled core proteins, regulate the formation and disassembly of pre-snoRNP intermediates, and control the activity of immature particles. The AAA+ ATPase RUVBL1 and RUVBL2 belong to the R2TP co-chaperones and play essential roles in snoRNP biogenesis, as well as in the formation of other macro-molecular complexes. Despite intensive research, their mechanisms of action are still incompletely understood.
Topics: Animals; Carrier Proteins; Coiled Bodies; HSP90 Heat-Shock Proteins; Humans; Multiprotein Complexes; Protein Binding; Protein Transport; RNA Processing, Post-Transcriptional; RNA, Small Nucleolar; Ribonucleoproteins, Small Nucleolar; Signal Transduction; Transcription, Genetic
PubMed: 27715451
DOI: 10.1080/15476286.2016.1243646 -
Nature Communications Nov 2023In the mammalian visual system, the ventral lateral geniculate nucleus (vLGN) of the thalamus receives salient visual input from the retina and sends prominent GABAergic...
In the mammalian visual system, the ventral lateral geniculate nucleus (vLGN) of the thalamus receives salient visual input from the retina and sends prominent GABAergic axons to the superior colliculus (SC). However, whether and how vLGN contributes to fundamental visual information processing remains largely unclear. Here, we report in mice that vLGN facilitates visually-guided approaching behavior mediated by the lateral SC and enhances the sensitivity of visual object detection. This can be attributed to the extremely broad spatial integration of vLGN neurons, as reflected in their much lower preferred spatial frequencies and broader spatial receptive fields than SC neurons. Through GABAergic thalamocollicular projections, vLGN specifically exerts prominent surround suppression of visuospatial processing in SC, leading to a fine tuning of SC preferences to higher spatial frequencies and smaller objects in a context-dependent manner. Thus, as an essential component of the central visual processing pathway, vLGN serves to refine and contextually modulate visuospatial processing in SC-mediated visuomotor behaviors via visually-driven long-range feedforward inhibition.
Topics: Mice; Animals; Geniculate Bodies; Neurons; Thalamus; Visual Pathways; Superior Colliculi; Mammals
PubMed: 37949869
DOI: 10.1038/s41467-023-43147-9 -
Frontiers in Plant Science 2022Phytochromes are red- and far-red light receptors that control the growth and development of plants, enabling them to respond adequately to changing light conditions. It...
Phytochromes are red- and far-red light receptors that control the growth and development of plants, enabling them to respond adequately to changing light conditions. It has been shown that halted mRNAs stored in RNA granules called processing bodies are released upon light perception and contribute to the adaptation to the light environment. However, the photophysiological background of this process is largely unknown. We found that light of different wavelengths can trigger the disassembly of processing bodies in a dose- and time-dependent manner. We show that phytochromes control this process in red- and far-red light and that cytoplasmic phytochrome A is sufficient and necessary for the far-red light-induced disassembly of processing bodies. This adds a novel, unexpected cytoplasmic function to the processes controlled by phytochrome A. Overall, our findings suggest a role of phytochromes in the control of translationally halted mRNAs that are stored in processing bodies. We expect our findings to facilitate understanding of how light and environmental cues control the assembly and disassembly of processing bodies, which could have broader implications for the regulation of non-membranous organelles in general.
PubMed: 35283917
DOI: 10.3389/fpls.2022.828529 -
Bioresources and Bioprocessing 2021The Global Diabetes Compact was launched by the World Health Organization in April 2021 with one of its important goals to increase the accessibility and affordability... (Review)
Review
The Global Diabetes Compact was launched by the World Health Organization in April 2021 with one of its important goals to increase the accessibility and affordability of life-saving medicine-insulin. The rising prevalence of diabetes worldwide is bound to escalate the demand for recombinant insulin therapeutics, and currently, the majority of recombinant insulin therapeutics are produced from inclusion bodies. Here, a comprehensive review of downstream processing of recombinant human insulin/analogue production from inclusion bodies is presented All the critical aspects of downstream processing, starting from proinsulin recovery from inclusion bodies, inclusion body washing, inclusion body solubilization and oxidative sulfitolysis, cyanogen bromide cleavage, buffer exchange, purification by chromatography, pH precipitation and zinc crystallization methods, proinsulin refolding, enzymatic cleavage, and formulation, are explained in this review. Pertinent examples are summarized and the practical aspects of integrating every procedure into a multimodal purification scheme are critically discussed. In the face of increasing global demand for insulin product, there is a pressing need to develop a more efficient and economical production process. The information presented would be insightful to all the manufacturers and stakeholders for the production of human insulins, insulin analogues or biosimilars, as they strive to make further progresses in therapeutic recombinant insulin development and production.
PubMed: 34336550
DOI: 10.1186/s40643-021-00419-w -
Nucleic Acids Research Dec 2020Eukaryotic cells compartmentalize their internal milieu in order to achieve specific reactions in time and space. This organization in distinct compartments is essential... (Review)
Review
Eukaryotic cells compartmentalize their internal milieu in order to achieve specific reactions in time and space. This organization in distinct compartments is essential to allow subcellular processing of regulatory signals and generate specific cellular responses. In the nucleus, genetic information is packaged in the form of chromatin, an organized and repeated nucleoprotein structure that is a source of epigenetic information. In addition, cells organize the distribution of macromolecules via various membrane-less nuclear organelles, which have gathered considerable attention in the last few years. The macromolecular multiprotein complexes known as Promyelocytic Leukemia Nuclear Bodies (PML NBs) are an archetype for nuclear membrane-less organelles. Chromatin interactions with nuclear bodies are important to regulate genome function. In this review, we will focus on the dynamic interplay between PML NBs and chromatin. We report how the structure and formation of PML NBs, which may involve phase separation mechanisms, might impact their functions in the regulation of chromatin dynamics. In particular, we will discuss how PML NBs participate in the chromatinization of viral genomes, as well as in the control of specific cellular chromatin assembly pathways which govern physiological mechanisms such as senescence or telomere maintenance.
Topics: Cell Nucleus; Cellular Senescence; Chromatin; Chromatin Assembly and Disassembly; Genome, Human; Genome, Viral; Histones; Host-Pathogen Interactions; Humans; Intranuclear Inclusion Bodies; Promyelocytic Leukemia Protein; Protein Processing, Post-Translational; Small Ubiquitin-Related Modifier Proteins; Sumoylation; Telomere Homeostasis; Viruses
PubMed: 33068409
DOI: 10.1093/nar/gkaa828 -
Revista de Neurologia Jan 2019Lafora disease is autosomal recessive progressive myoclonus epilepsy with late childhood-to teenage-onset caused by loss-of-function mutations in either EPM2A or EPM2B... (Review)
Review
INTRODUCTION
Lafora disease is autosomal recessive progressive myoclonus epilepsy with late childhood-to teenage-onset caused by loss-of-function mutations in either EPM2A or EPM2B genes encoding laforin or malin, respectively.
DEVELOPMENT
The main symptoms of Lafora disease, which worsen progressively, are: myoclonus, occipital seizures, generalized tonic-clonic seizures, cognitive decline, neuropsychiatric syptoms and ataxia with a fatal outcome. Pathologically, Lafora disease is characterized by the presence of polyglucosans deposits (named Lafora bodies), in the brain, liver, muscle and sweat glands. Diagnosis of Lafora disease is made through clinical, electrophysiological, histological and genetic findings. Currently, there is no treatment to cure or prevent the development of the disease. Traditionally, antiepileptic drugs are used for the management of myoclonus and seizures. However, patients become drug-resistant after the initial stage.
CONCLUSIONS
Lafora disease is a rare pathology that has serious consequences for patients and their caregivers despite its low prevalence. Therefore, continuing research in order to clarify the underlying mechanisms and hopefully developing new palliative and curative treatments for the disease is necessary.
Topics: Animals; Anticonvulsants; Brain; Combined Modality Therapy; Disease Progression; Drug Resistance; Glucans; Humans; Inclusion Bodies; Lafora Disease; Mice; Mice, Knockout; Palliative Care; Protein Processing, Post-Translational; Protein Tyrosine Phosphatases, Non-Receptor; Psychotherapy; Social Support; Ubiquitin-Protein Ligases; Ubiquitination; Vagus Nerve Stimulation
PubMed: 30638256
DOI: No ID Found -
Brain Sciences Jan 2023Body inversion effects (BIEs) reflect the deployment of the configural processing of body stimuli. BIE modulates the activity of body-selective areas within both the...
Body inversion effects (BIEs) reflect the deployment of the configural processing of body stimuli. BIE modulates the activity of body-selective areas within both the dorsal and the ventral streams, which are tuned to low (LSF) or high spatial frequencies (HSF), respectively. The specific contribution of different bands to the configural processing of bodies along gender and posture dimensions, however, is still unclear. Seventy-two participants performed a delayed matching-to-sample paradigm in which upright and inverted bodies, differing for gender or posture, could be presented in their original intact form or in the LSF- or HSF-filtered version. In the gender discrimination task, participants' performance was enhanced by the presentation of HSF images. Conversely, for the posture discrimination task, a better performance was shown for either HSF or LSF images. Importantly, comparing the amount of BIE across spatial-frequency conditions, we found greater BIEs for HSF than LSF images in both tasks, indicating that configural body processing may be better supported by HSF information, which will bias processing in the ventral stream areas. Finally, the exploitation of HSF information for the configural processing of body postures was lower in individuals with higher autistic traits, likely reflecting a stronger reliance on the local processing of body-part details.
PubMed: 36831733
DOI: 10.3390/brainsci13020190 -
International Journal of Health Policy... Jul 2022Food systems affect nutritional and other health outcomes. Recent literature from India has described policy aspects addressing nutritional implications of specific... (Review)
Review
BACKGROUND
Food systems affect nutritional and other health outcomes. Recent literature from India has described policy aspects addressing nutritional implications of specific foods (eg, fruits, vegetables, and trans-fats), and identified opportunities to tackle the double burden of malnutrition. This paper attempts to deepen the understanding on how health concerns and the role of the health sector are addressed across food systems policies in India.
METHODS
This qualitative study used two approaches; namely (i) the framework method and (ii) manifest content analysis, to investigate national-level policy documents from relevant sectors (ie, food security, agriculture, biodiversity, food processing, trade, and waste management, besides health and nutrition). The documents were selected purposively. The textual data were coded and compared, from which themes were identified, described, and interpreted. Additionally, mentions of various health concerns and of the health ministry in the included documents were recorded and collated.
RESULTS
A total of 35 policy documents were included in the analysis. A variety of health concerns spanning nutritional, communicable and non-communicable diseases (NCDs) were mentioned. Undernutrition received specific attention even beyond nutrition policies. Only few policies mentioned NCDs, infectious diseases, and injuries. Governing and advisory bodies were instituted by 17 of the analysed policies (eg, food safety, agriculture, and food processing), and often included representation from the health ministry (9 of the 17 identified inter-ministerial bodies).
CONCLUSION
We found some evidence of concern for health, and inclusion of health ministry in food policy documents in India. The ongoing and planned intersectoral coordination to tackle undernutrition could inform actions to address other relevant but currently underappreciated concerns such as NCDs. Our study demonstrated a method for analysis of health consideration and intersectoral coordination in food policy documents, which could be applied to studies in other settings and policy domains.
Topics: Humans; Health Policy; India; Malnutrition; Nutrition Policy; Nutritional Status; Policy Making
PubMed: 33904697
DOI: 10.34172/ijhpm.2021.18 -
Signal Transduction and Targeted Therapy Apr 2024RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the...
RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.
Topics: Humans; Autophagy; Colorectal Neoplasms; Family; Phosphoproteins; Proteins; RNA; RNA, Circular; RNA-Binding Proteins
PubMed: 38565536
DOI: 10.1038/s41392-024-01787-3