scholarly journals Triblock copolymer micelle model of spherical paraspeckles

2020 ◽  
Author(s):  
Tetsuya Yamamoto ◽  
Tomohiro Yamazaki ◽  
Tetsuro Hirose
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Threshold Value ◽  
Critical Value ◽  
Nuclear Bodies ◽  
Transcription Rate ◽  
Abc Triblock Copolymers ◽  
The Core ◽  
In The Wild ◽  
Copolymer Micelle

ABSTRACTParaspeckles are nuclear bodies composed of architectural RNA (arcRNA) and RNA-binding proteins. In the wild type, the blocks at the two terminal regions of arcRNAs compose the shell of paraspeckles and the middle region between the two terminal blocks composes the core, analogous to micelles of ABC triblock copolymers. We here use an extension of the theory of polymer micelles to predict the structure and size of paraspeckles as one decreases the length of one of the terminal blocks of arcRNA by CRISPR/Cas9, assuming that paraspeckles are spherical. Our theory predicts that when the length of the edited terminal blocks is larger than a critical value, paraspeckles show discontinuous transitions between the structure in which all the edited terminal blocks are localized in the shell and the structure in which all the edited terminal blocks are localized in the core at a threshold value of the transcription rate of arcRNA. In contrast, when the length of the edited terminal blocks is smaller than the critical value, the population of edited terminal blocks in the shell decreases continuously as one increases the transcription rate of arcRNA. The size of paraspeckles increases as one decreases the length of the edited terminal blocks. These predictions are consistent with our experiments.

scholarly journals Lin28, a major translation reprogramming factor, gains access to YB-1-packaged mRNA through its cold-shock domain

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Anastasiia Samsonova ◽  
Krystel El Hage ◽  
Bénédicte Desforges ◽  
Vandana Joshi ◽  
Marie-Jeanne Clément ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Cold Shock ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Binding Protein ◽  
Large Set ◽  
Core Component ◽  
The Core ◽  
Cold Shock Domain ◽  
Global Translation

AbstractThe RNA-binding protein Lin28 (Lin28a) is an important pluripotency factor that reprograms translation and promotes cancer progression. Although Lin28 blocks let-7 microRNA maturation, Lin28 also binds to a large set of cytoplasmic mRNAs directly. However, how Lin28 regulates the processing of many mRNAs to reprogram global translation remains unknown. We show here, using a structural and cellular approach, a mixing of Lin28 with YB-1 (YBX1) in the presence of mRNA owing to their cold-shock domain, a conserved β-barrel structure that binds to ssRNA cooperatively. In contrast, the other RNA binding-proteins without cold-shock domains tested, HuR, G3BP-1, FUS and LARP-6, did not mix with YB-1. Given that YB-1 is the core component of dormant mRNPs, a model in which Lin28 gains access to mRNPs through its co-association with YB-1 to mRNA may provide a means for Lin28 to reprogram translation. We anticipate that the translational plasticity provided by mRNPs may contribute to Lin28 functions in development and adaptation of cancer cells to an adverse environment.

scholarly journals The Drosophila RNA binding protein Nab2 patterns dendritic arbors and axons via the planar cell polarity pathway

2021 ◽  
Author(s):  
Kenneth H. Moberg ◽  
Edwin B. Corgiat ◽  
Sara List ◽  
J. Christopher Rounds ◽  
Dehong Yu ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Axon Growth ◽  
Planar Cell Polarity Pathway ◽  
Translational Repressor ◽  
The Core ◽  
Dendritic Arbors ◽  
Axon Projection

RNA binding proteins support neurodevelopment by modulating numerous steps in post-transcriptional regulation, including splicing, export, translation, and turnover of mRNAs that can traffic into axons and dendrites. One such RBP is ZC3H14, which is lost in an inherited intellectual disability. The Drosophila melanogaster ZC3H14 ortholog, Nab2, localizes to neuronal nuclei and cytoplasmic ribonucleoprotein granules, and is required for olfactory memory and proper axon projection into brain mushroom bodies. Nab2 can act as a translational repressor in conjunction with the Fragile-X mental retardation protein homolog Fmr1 and shares target RNAs with the Fmr1-interacting RBP Ataxin-2. However, neuronal signaling pathways regulated by Nab2 and their potential roles outside of mushroom body axons remain undefined. Here, we demonstrate that Nab2 restricts branching and projection of larval sensory dendrites via the planar cell polarity pathway, and that this link may provide a conserved mechanism through which Nab2/ZC3H14 modulates projection of both axons and dendrites. Planar cell polarity proteins are enriched in a Nab2-regulated brain proteomic dataset. Complementary genetic data indicate that Nab2 guides dendrite and axon growth through the planar-cell-polarity pathway. Analysis of the core planar cell polarity protein Vang, which is depleted in the Nab2 mutant whole-brain proteome, uncovers selective and dramatic loss of Vang within axon/dendrite-enriched brain neuropil relative to brain regions containing cell bodies. Collectively, these data demonstrate that Nab2 regulates dendritic arbors and axon projection by a planar-cell-polarity-linked mechanism and identify Nab2 as required for accumulation of the core planar cell polarity factor Vang in distal neuronal projections.

scholarly journals Pan-cancer analysis of RNA binding proteins (RBPs) reveals the involvement of the core pre-mRNA splicing and translation machinery in tumorigenesis

2018 ◽  
Author(s):  
Bin Zhang ◽  
Kamesh R. Babu ◽  
Chun You Lim ◽  
Zhi Hao Kwok ◽  
Jia Li ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Copy Number ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Human Cancer ◽  
Mrna Splicing ◽  
Regulatory Mechanisms ◽  
Translation Machinery ◽  
The Core ◽  
Cancer Types

AbstractRNA binding proteins (RBPs) are key regulators of posttranscriptional processes such as RNA maturation, transport, localization, turnover and translation. Despite their dysregulation in various diseases including cancer, the landscape of RBP expression and regulatory mechanisms in human cancer has not been well characterized. Here, we analyzed mRNA expression of 1487 RBPs in ~6700 clinical samples across 16 human cancer types and found that there were significantly more upregulated RBPs than downregulated ones in tumors when compared to their adjacent normal tissues. Across almost all of the 16 cancer types, 109 RBPs were consistently upregulated (cuRBPs) while only 41 RBPs were consistently downregulated (cdRBPs). Integrating expression with the copy number and DNA methylation data, we found that the overexpression of cuRBPs is largely associated with the amplification of copy number, whereas the downregulation of cdRBPs may be a result of epigenetic silencing mediated by DNA methylation. Furthermore, our results indicated that cuRBPs could work together to promote cancer progression potentially through the involvement of splicing and translation machinery, while cdRBPs might function independently to suppress tumorigenesis. Additionally, we focused on colon cancer and identified several novel potential oncogenic RBPs, such as PABPC1L which might promote cancer development via regulating the core splicing machinery. In summary, we showed distinct expression landscapes, regulatory mechanisms and characteristics of cuRBPs and cdRBPs and implicated several novel RBPs in cancer pathogenesis. Moreover, our results suggest that the involvement of the core pre-mRNA splicing and translation machinery could be critical in tumorigenesis.

Stressful initiations

2002 ◽  
Vol 115 (16) ◽  
pp. 3227-3234 ◽  
Author(s):  
Paul Anderson ◽  
Nancy Kedersha
Keyword(s):  
Environmental Stress ◽  
Uv Irradiation ◽  
Ternary Complex ◽  
Rna Binding ◽  
Dynamic Equilibrium ◽  
Rna Binding Proteins ◽  
Ribosomal Subunit ◽  
Eukaryotic Cells ◽  
Translational Initiation ◽  
The Core

Stress granules (SGs) are phase-dense particles that appear in the cytoplasm of eukaryotic cells that have been exposed to environmental stress(e.g. heat, oxidative conditions, hyperosmolarity and UV irradiation). SG assembly is a consequence of abortive translational initiation: SGs appear when translation is initiated in the absence of eIF2-GTP-tRNAiMet, the ternary complex that normally loads tRNAiMet onto the small ribosomal subunit. Stress-induced depletion of eIF2-GTP-tRNAiMet allows the related RNA-binding proteins TIA-1 and TIAR to promote the assembly of eIF2-eIF5-deficient preinitiation complexes, the core constituents of SGs. The mRNP components that make up the SG are in a dynamic equilibrium with polysomes. As such, the SG appears to constitute a metabolic domain through which mRNPs are continually routed and subjected to triage — they are first monitored for integrity and composition, and then sorted for productive translational initiation or targeted degradation.

scholarly journals EBV noncoding RNA EBER2 interacts with host RNA-binding proteins to regulate viral gene expression

2016 ◽  
Vol 113 (12) ◽  
pp. 3221-3226 ◽  
Author(s):  
Nara Lee ◽  
Therese A. Yario ◽  
Jessica S. Gao ◽  
Joan A. Steitz
Keyword(s):  
Gene Expression ◽  
Noncoding Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Lytic Replication ◽  
Nuclear Bodies ◽  
Viral Gene ◽  
Mrna Levels ◽  
Binding Studies

Epstein–Barr virus (EBV) produces a highly abundant noncoding RNA called EBV-encoded RNA 2 (EBER2) that interacts indirectly with the host transcription factor paired box protein 5 (PAX5) to regulate viral latent membrane protein 1/2 (LMP1/2) gene expression as well as EBV lytic replication. To identify intermediary proteins, we isolated EBER2–PAX5-containing complexes and analyzed the protein components by mass spectrometry. The top candidates include three host proteins splicing factor proline and glutamine rich (SFPQ), non-POU domain-containing octamer-binding protein (NONO), and RNA binding motif protein 14 (RBM14), all reported to be components of nuclear bodies called paraspeckles. In vivo RNA–protein crosslinking indicates that SFPQ and RBM14 contact EBER2 directly. Binding studies using recombinant proteins demonstrate that SFPQ and NONO associate with PAX5, potentially bridging its interaction with EBER2. Similar to EBER2 or PAX5 depletion, knockdown of any of the three host RNA-binding proteins results in the up-regulation of viral LMP2A mRNA levels, supporting a physiologically relevant interaction of these newly identified factors with EBER2 and PAX5. Identification of these EBER2-interacting proteins enables the search for cellular noncoding RNAs that regulate host gene expression in a manner similar to EBER2.

scholarly journals The Sam68 nuclear body is composed of two RNase-sensitive substructures joined by the adaptor HNRNPL

2016 ◽  
Vol 214 (1) ◽  
pp. 45-59 ◽  
Author(s):  
Taro Mannen ◽  
Seisuke Yamashita ◽  
Kozo Tomita ◽  
Naoki Goshima ◽  
Tetsuro Hirose
Keyword(s):  
Cell Nucleus ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nuclear Body ◽  
Nuclear Bodies ◽  
Cdna Clones ◽  
Rna Recognition ◽  
Rna Recognition Motifs ◽  
Rnase Treatment ◽  
Recognition Motifs

The mammalian cell nucleus contains membraneless suborganelles referred to as nuclear bodies (NBs). Some NBs are formed with an architectural RNA (arcRNA) as the structural core. Here, we searched for new NBs that are built on unidentified arcRNAs by screening for ribonuclease (RNase)-sensitive NBs using 32,651 fluorescently tagged human cDNA clones. We identified 32 tagged proteins that required RNA for their localization in distinct nuclear foci. Among them, seven RNA-binding proteins commonly localized in the Sam68 nuclear body (SNB), which was disrupted by RNase treatment. Knockdown of each SNB protein revealed that SNBs are composed of two distinct RNase-sensitive substructures. One substructure is present as a distinct NB, termed the DBC1 body, in certain conditions, and the more dynamic substructure including Sam68 joins to form the intact SNB. HNRNPL acts as the adaptor to combine the two substructures and form the intact SNB through the interaction of two sets of RNA recognition motifs with the putative arcRNAs in the respective substructures.

Paraspeckles: possible nuclear hubs by the RNA for the RNA

2012 ◽  
Vol 3 (5) ◽  
pp. 415-428 ◽  
Author(s):  
Tetsuro Hirose ◽  
Shinichi Nakagawa
Keyword(s):  
Rna Binding ◽  
Cultured Cells ◽  
Rna Binding Proteins ◽  
Nuclear Body ◽  
Nuclear Bodies ◽  
Mouse Tissue ◽  
Nuclear Retention ◽  
Selective Stabilization ◽  
Essential Components ◽  
And Function

AbstractThe mammalian cell nucleus is a highly compartmentalized system in which multiple subnuclear structures, called nuclear bodies, exist in the nucleoplasmic spaces. Some of the nuclear bodies contain specific long non-coding RNAs (ncRNAs) as their components, and may serve as sites for long ncRNA functions that remain largely enigmatic. A paraspeckle is a nuclear body that is almost ubiquitously observed in mammalian cultured cells but is cell population-specific in adult mouse tissue. The paraspeckle structure is RNase-sensitive. Long ncRNAs, termed MENε/β ncRNAs (also referred to as NEAT1 ncRNAs), have been identified as the RNA components of the paraspeckles. Specific elimination has revealed that MENε/β ncRNAs are essential components for the formation of the intact paraspeckle structure. Paraspeckle formation requires the continual MENε/β ncRNA biogenesis process, including ongoing transcription, alternative 3′-end processing, and stabilization. Some paraspeckle-localized RNA-binding proteins (p54/nrb and PSF) direct paraspeckle formation through the selective stabilization of MENβ ncRNA. Both MENε/β ncRNA expression and their subsequent interactions with paraspeckle proteins can be regulated under environmental and developmental conditions, which are reflected in the size and number of the paraspeckles. However, how paraspeckles function remains largely unsolved. Paraspeckles appear to serve as the site of nuclear retention of specific mRNAs that are selectively transported to the cytoplasm upon certain signals. Alternatively, MENε/β ncRNAs may sequester paraspeckle proteins that function outside the paraspeckles. This review focuses on known aspects of paraspeckles and provides a model of their structure and function.

scholarly journals LncRNA-dependent nuclear stress bodies promote intron retention through SR protein phosphorylation

2019 ◽  
Author(s):  
Kensuke Ninomiya ◽  
Shungo Adachi ◽  
Tohru Natsume ◽  
Junichi Iwakiri ◽  
Goro Terai ◽  
...  
Keyword(s):  
Thermal Stress ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Intron Retention ◽  
Nuclear Bodies ◽  
Splicing Factors ◽  
Stress Recovery ◽  
Stress Exposure ◽  
Sr Protein ◽  
Retained Introns

AbstractA number of long noncoding RNAs (lncRNAs) are induced in response to specific stresses to construct membrane-less nuclear bodies; however, their function remains poorly understood. Here, we report the role of nuclear stress bodies (nSBs) formed on highly repetitive satellite III (HSATIII) lncRNAs derived from primate-specific satellite III repeats upon thermal stress exposure. A transcriptomic analysis revealed that depletion of HSATIII lncRNAs, resulting in elimination of nSBs, promoted splicing of 533 retained introns during thermal stress recovery. A HSATIII-Comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS) analysis identified multiple splicing factors in nSBs, including serine and arginine-rich pre-mRNA splicing factors (SRSFs), the phosphorylation states of which affect splicing patterns. SRSFs are rapidly dephosphorylated upon thermal stress exposure. During stress recovery, CDC like kinase 1 (CLK1) was recruited to nSBs and accelerated the re-phosphorylation of SRSF9, thereby promoting target intron retention. Our findings suggest that HSATIII-dependent nSBs serve as a conditional platform for phosphorylation of SRSFs by CLK1 to promote the rapid adaptation of gene expression through intron retention following thermal stress exposure.

scholarly journals Architectural RNA in chromatin organization

2020 ◽  
Vol 48 (5) ◽  
pp. 1967-1978
Author(s):  
Jitendra Thakur ◽  
Steven Henikoff
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Ribonuclease A ◽  
Rnase A ◽  
Chromatin Organization ◽  
Nuclear Bodies ◽  
Non Coding Rnas ◽  
Rna Depletion

RNA plays a well-established architectural role in the formation of membraneless interchromatin nuclear bodies. However, a less well-known role of RNA is in organizing chromatin, whereby specific RNAs have been found to recruit chromatin modifier proteins. Whether or not RNA can act as an architectural molecule for chromatin remains unclear, partly because dissecting the architectural role of RNA from its regulatory role remains challenging. Studies that have addressed RNA's architectural role in chromatin organization rely on in situ RNA depletion using Ribonuclease A (RNase A) and suggest that RNA plays a major direct architectural role in chromatin organization. In this review, we will discuss these findings, candidate chromatin architectural long non-coding RNAs and possible mechanisms by which RNA, along with RNA binding proteins might be mediating chromatin organization.

scholarly journals Circadian RNA expression elicited by 3’-UTR IRAlu-paraspeckle associated elements

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Manon Torres ◽  
Denis Becquet ◽  
Marie-Pierre Blanchard ◽  
Séverine Guillen ◽  
Bénédicte Boyer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nuclear Bodies ◽  
Transcriptional Level ◽  
Pituitary Cells ◽  
Nuclear Retention ◽  
Circadian Expression ◽  
Expression Control ◽  
Non Coding Rna

Paraspeckles are nuclear bodies form around the long non-coding RNA, Neat1, and RNA-binding proteins. While their role is not fully understood, they are believed to control gene expression at a post-transcriptional level by means of the nuclear retention of mRNA containing in their 3’-UTR inverted repeats of Alu sequences (IRAlu). In this study, we found that, in pituitary cells, all components of paraspeckles including four major proteins and Neat1 displayed a circadian expression pattern. Furthermore the insertion of IRAlu at the 3’-UTR of the EGFP cDNA led to a rhythmic circadian nuclear retention of the egfp mRNA that was lost when paraspeckles were disrupted whereas insertion of a single antisense Alu had only a weak effect. Using real-time video-microscopy, these IRAlu were further shown to drive a circadian expression of EGFP protein. This study shows that paraspeckles, thanks to their circadian expression, control circadian gene expression at a post-transcriptional level.

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