scholarly journals Core spliceosomal Sm proteins as constituents of cytoplasmic mRNPs in plants

2019 ◽  
Author(s):  
Malwina Hyjek-Składanowska ◽  
Mateusz Bajczyk ◽  
Marcin Gołębiewski ◽  
Przemysław Nuc ◽  
Agnieszka Kołowerzo-Lubnau ◽  
...  
Keyword(s):  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Mrna Splicing ◽  
Sm Proteins ◽  
Cytoplasmic Bodies ◽  
Evolutionarily Conserved ◽  
Processing Steps

ABSTRACTIn light of recent studies, many of the cytoplasmic posttranscriptional mRNA processing steps take place in highly specialized microdomains referred to as cytoplasmic bodies. These evolutionarily conserved microdomains are sites of regulation for both mRNA translation and degradation. It has been shown that in the larch microsporocyte cytoplasm, there is a significant pool of Sm proteins not related to snRNP complexes. These Sm proteins accumulate within distinct cytoplasmic bodies (S-bodies) that also contain mRNA. Sm proteins constitute an evolutionarily ancient family of small RNA-binding proteins. In eukaryotic cells, these molecules are involved in pre-mRNA splicing. The latest research indicates that in addition to this well-known function, Sm proteins could also have an impact on mRNA at subsequent stages of its life cycle. The aim of this work was to verify the hypothesis that canonical Sm proteins are part of the cytoplasmic mRNP complex and thus function in the posttranscriptional regulation of gene expression in plants.

scholarly journals RNA-binding proteins La and HuR cooperatively modulate translation repression of PDCD4 mRNA

2020 ◽  
pp. jbc.RA120.014894
Author(s):  
Ravi Kumar ◽  
Dipak Kumar Poria ◽  
Partho Sarothi Ray
Keyword(s):  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Suppressor Gene ◽  
Cooperative Action ◽  
Translation Repression

Post-transcriptional regulation of gene expression plays a critical role in controlling the inflammatory response. An uncontrolled inflammatory response results in chronic inflammation, often leading to tumorigenesis. Programmed cell death 4 (PDCD4) is a pro-inflammatory tumor-suppressor gene which helps to prevent the transition from chronic inflammation to cancer. PDCD4 mRNA translation is regulated by an interplay between the oncogenic microRNA miR-21 and the RNA-binding protein (RBP) HuR in response to LPS stimulation, but the role of other regulatory factors remain unknown. Here we report that the RBP Lupus antigen (La) interacts with the 3’UTR of PDCD4 mRNA and prevents miR-21-mediated translation repression. While LPS causes nuclear-cytoplasmic translocation of HuR, it enhances cellular La expression. Remarkably, La and HuR were found to bind cooperatively to the PDCD4 mRNA and mitigate miR-21-mediated translation repression. The cooperative action of La and HuR reduced cell proliferation and enhanced apoptosis, reversing the pro-oncogenic function of miR-21. Together, these observations demonstrate a cooperative interplay between two RBPs, triggered differentially by the same stimulus, which exerts a synergistic effect on PDCD4 expression and thereby helps maintain a balance between inflammation and tumorigenesis.

scholarly journals Two Yeast La Motif-containing Proteins Are RNA-binding Proteins that Associate with Polyribosomes

1999 ◽  
Vol 10 (11) ◽  
pp. 3849-3862 ◽  
Author(s):  
Suzanne G. Sobel ◽  
Sandra L. Wolin
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Polymerase Iii ◽  
Mrna Translation ◽  
Protein Synthesis Inhibitors ◽  
La Protein ◽  
Evolutionarily Conserved ◽  
Synthetically Lethal ◽  
Type Strains

We have characterized two Saccharomyces cerevisiaeproteins, Sro9p and Slf1p, which contain a highly conserved motif found in all known La proteins. Originally described as an autoantigen in patients with rheumatic disease, the La protein binds to newly synthesized RNA polymerase III transcripts. In yeast, the La protein homologue Lhp1p is required for the normal pathway of tRNA maturation and also stabilizes newly synthesized U6 RNA. We show that deletions in both SRO9 and SLF1 are not synthetically lethal with a deletion in LHP1, indicating that the three proteins do not function in a single essential process. Indirect immunofluorescence microscopy reveals that although Lhp1p is primarily localized to the nucleus, Sro9p is cytoplasmic. We demonstrate that Sro9p and Slf1p are RNA-binding proteins that associate preferentially with translating ribosomes. Consistent with a role in translation, strains lacking either Sro9p or Slf1p are less sensitive than wild-type strains to certain protein synthesis inhibitors. Thus, Sro9p and Slf1p define a new and possibly evolutionarily conserved class of La motif-containing proteins that may function in the cytoplasm to modulate mRNA translation.

HuR and other turnover- and translation-regulatory RNA-binding proteins: implications for the kidney

2014 ◽  
Vol 306 (6) ◽  
pp. F569-F576 ◽  
Author(s):  
Rudolf Pullmann ◽  
Hamid Rabb
Keyword(s):  
Posttranscriptional Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Matrix Remodeling ◽  
Acid Base Balance ◽  
Renal Metabolism

The posttranscriptional regulation of gene expression occurs through cis RNA regulatory elements by the action of trans factors, which are represented by noncoding RNAs (especially microRNAs) and turnover- and translation-regulatory (TTR) RNA-binding proteins (RBPs). These multifactorial proteins are a group of heterogeneous RBPs primarily implicated in controlling the decay and translation rates of target mRNAs. TTR-RBPs usually shuttle between cellular compartments (the nucleus and cytoplasm) in response to various stimuli and undergo posttranslational modifications such as phosphorylation or methylation to ensure their proper subcellular localization and function. TTR-RBPs are emerging as key regulators of a wide variety of genes influencing kidney physiology and pathology. This review summarizes the current knowledge of TTR-RBPs that influence renal metabolism. We will discuss the role of TTR-RBPs as regulators of kidney ischemia, fibrosis and matrix remodeling, angiogenesis, membrane transport, immunity, vascular tone, hypertension, and acid-base balance as well as anemia, bone mineral disease, and vascular calcification.

scholarly journals RNA granules

2006 ◽  
Vol 172 (6) ◽  
pp. 803-808 ◽  
Author(s):  
Paul Anderson ◽  
Nancy Kedersha
Keyword(s):  
Messenger Rna ◽  
Posttranscriptional Regulation ◽  
Spatial Organization ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Processing Bodies ◽  
Rna Granules ◽  
Cytoplasmic Rna ◽  
Messenger Rna Translation

Cytoplasmic RNA granules in germ cells (polar and germinal granules), somatic cells (stress granules and processing bodies), and neurons (neuronal granules) have emerged as important players in the posttranscriptional regulation of gene expression. RNA granules contain various ribosomal subunits, translation factors, decay enzymes, helicases, scaffold proteins, and RNA-binding proteins, and they control the localization, stability, and translation of their RNA cargo. We review the relationship between different classes of these granules and discuss how spatial organization regulates messenger RNA translation/decay.

scholarly journals RNA Recognition and Immunity—Innate Immune Sensing and Its Posttranscriptional Regulation Mechanisms

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1701
Author(s):  
Takuya Uehata ◽  
Osamu Takeuchi
Keyword(s):  
Nuclear Export ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Inflammatory Responses ◽  
Rna Binding Proteins ◽  
Mammalian Species ◽  
Regulation Of Gene Expression ◽  
Innate Immune ◽  
Type I ◽  
Immune Sensing

RNA acts as an immunostimulatory molecule in the innate immune system to activate nucleic acid sensors. It functions as an intermediate, conveying genetic information to control inflammatory responses. A key mechanism for RNA sensing is discriminating self from non-self nucleic acids to initiate antiviral responses reliably, including the expression of type I interferon (IFN) and IFN-stimulated genes. Another important aspect of the RNA-mediated inflammatory response is posttranscriptional regulation of gene expression, where RNA-binding proteins (RBPs) have essential roles in various RNA metabolisms, including splicing, nuclear export, modification, and translation and mRNA degradation. Recent evidence suggests that the control of mRNA stability is closely involved in signal transduction and orchestrates immune responses. In this study, we review the current understanding of how RNA is sensed by host RNA sensing machinery and discuss self/non-self-discrimination in innate immunity focusing on mammalian species. Finally, we discuss how posttranscriptional regulation by RBPs shape immune reactions.

scholarly journals Involvement of a tissue-specific RNA recognition motif protein in Drosophila spermatogenesis.

1997 ◽  
Vol 17 (5) ◽  
pp. 2708-2715 ◽  
Author(s):  
S R Haynes ◽  
M T Cooper ◽  
S Pype ◽  
D T Stolow
Keyword(s):  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Protein Gene ◽  
Germ Line ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Two Dimensional Gel Electrophoresis ◽  
Recognition Motif

RNA binding proteins mediate posttranscriptional regulation of gene expression via their roles in nuclear and cytoplasmic mRNA metabolism. Many of the proteins involved in these processes have a common RNA binding domain, the RNA recognition motif (RRM). We have characterized the Testis-specific RRM protein gene (Tsr), which plays an important role in spermatogenesis in Drosophila melanogaster. Disruption of Tsr led to a dramatic reduction in male fertility due to the production of spermatids with abnormalities in mitochondrial morphogenesis. Tsr is located on the third chromosome at 87F, adjacent to the nuclear pre-mRNA binding protein gene Hrb87F. A 1.7-kb Tsr transcript was expressed exclusively in the male germ line. It encoded a protein containing two RRMs similar to those found in HRB87F as well as a unique C-terminal domain. TSR protein was located in the cytoplasm of spermatocytes and young spermatids but was absent from mature sperm. The cellular proteins expressed in premeiotic primary spermatocytes from Tsr mutant and wild-type males were assessed by two-dimensional gel electrophoresis. Lack of TSR resulted in the premature expression of a few proteins prior to meiosis; this was abolished by a transgenic copy of Tsr. These data demonstrate that TSR negatively regulated the expression of some testis proteins and, in combination with its expression pattern and subcellular localization, suggest that TSR regulates the stability or translatability of some mRNAs during spermatogenesis.

scholarly journals A Musashi-Related Protein is Essential for Gametogenesis in Arabidopsis

2019 ◽  
Author(s):  
Laura A. Moody ◽  
Ester Rabbinowitsch ◽  
Hugh G. Dickinson ◽  
Roxaana Clayton ◽  
David M. Emms ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Pollen Viability ◽  
Functional Characterization ◽  
Mrna Translation ◽  
High Rate ◽  
Loss Of Function ◽  
Gametophyte Development ◽  
Evolutionarily Conserved ◽  
Related Proteins

SUMMARYMusashi (Msi) proteins are an evolutionarily conserved group of RNA-binding proteins, required for targeted control of mRNA translation during many important developmental processes in animals. Most notably, Msi proteins play important roles during both spermatogenesis and oogenesis. Msi proteins also exist in plants but these are largely uncharacterized. Here we report the functional characterization of an Arabidopsis Msi orthologABORTED GAMETOPHYTE 2(AOG2), which encodes a protein containing two RNA recognition motifs and an ER-targeting signal. AOG2-GFP translational fusions were localized to the ER in transient assays, suggesting that AOG2 most likely binds to ER-targeted mRNAs. We show that disruptedAOG2function leads to a high rate of both ovule and seed abortion, and that homozygous loss of function mutants are embryo lethal. Furthermore, we demonstrate thatAOG2is required to establish asymmetry during pollen mitosis I, and that loss ofAOG2function leads to loss of pollen viability. Collectively the results reveal that AOG2 is required for the establishment of polarity and/or the progression of mitosis during gametophyte development in Arabidopsis, and thus Msi-related proteins have an evolutionarily conserved role in gametogenesis in both animals and plants.SIGNIFICANCE STATEMENTABORTED GAMETOPHYTE 2(AOG2) encodes a Musashi-related RNA-binding protein that is required for gametogenesis and embryogenesis in Arabidopsis.AOG2is required for the establishment of polarity and/or the progression of mitosis during gametophyte development in Arabidopsis, and thus Musashi-related proteins have an evolutionarily conserved role in gametogenesis in both animals and plants.

scholarly journals The DAZL and PABP families: RNA-binding proteins with interrelated roles in translational control in oocytes

Reproduction ◽  
2009 ◽  
Vol 137 (4) ◽  
pp. 595-617 ◽  
Author(s):  
Matthew Brook ◽  
Joel W S Smith ◽  
Nicola K Gray
Keyword(s):  
Gene Expression ◽  
Germ Cells ◽  
Translational Control ◽  
Translational Regulation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor

Gametogenesis is a highly complex process that requires the exquisite temporal, spatial and amplitudinal regulation of gene expression at multiple levels. Translational regulation is important in a wide variety of cell types but may be even more prevalent in germ cells, where periods of transcriptional quiescence necessitate the use of post-transcriptional mechanisms to effect changes in gene expression. Consistent with this, studies in multiple animal models have revealed an essential role for mRNA translation in the establishment and maintenance of reproductive competence. While studies in humans are less advanced, emerging evidence suggests that translational regulation plays a similarly important role in human germ cells and fertility. This review highlights specific mechanisms of translational regulation that play critical roles in oogenesis by activating subsets of mRNAs. These mRNAs are activated in a strictly determined temporal manner via elements located within their 3′UTR, which serve as binding sites fortrans-acting factors. While we concentrate on oogenesis, these regulatory events also play important roles during spermatogenesis. In particular, we focus on the deleted in azoospermia-like (DAZL) family of proteins, recently implicated in the translational control of specific mRNAs in germ cells; their relationship with the general translation initiation factor poly(A)-binding protein (PABP) and the process of cytoplasmic mRNA polyadenylation.

scholarly journals The Bic-C Family of Developmental Translational Regulators

2012 ◽  
Vol 2012 ◽  
pp. 1-23 ◽  
Author(s):  
Chiara Gamberi ◽  
Paul Lasko
Keyword(s):  
Developmental Biology ◽  
Human Disease ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Mrna Translation ◽  
Protein Translation ◽  
Model Organisms ◽  
Founding Member ◽  
Evolutionarily Conserved ◽  
Translational Regulators

Regulation of mRNA translation is especially important during cellular and developmental processes. Many evolutionarily conserved proteins act in the context of multiprotein complexes and modulate protein translation both at the spatial and the temporal levels. Among these, Bicaudal C constitutes a family of RNA binding proteins whose founding member was first identified inDrosophilaand contains orthologs in vertebrates. We discuss recent advances towards understanding the functions of these proteins in the context of the cellular and developmental biology of many model organisms and their connection to human disease.

scholarly journals STAU2 protein level is controlled by caspases and the CHK1 pathway and regulates cell cycle progression in the non-transformed hTERT-RPE1 cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lionel Condé ◽  
Yulemi Gonzalez Quesada ◽  
Florence Bonnet-Magnaval ◽  
Rémy Beaujois ◽  
Luc DesGroseillers
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Steady State ◽  
Posttranscriptional Regulation ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Cycle Progression

AbstractBackgroundStaufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from theSTAU2gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation.ResultsCRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway for 4 h dissociates STAU2 from proteins involved in translation and RNA metabolism.ConclusionsThese results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. The mechanism by which STAU2 regulates cell growth likely involves caspases and the kinase CHK1 pathway.

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