scholarly journals RNA-Binding Proteins Hold Key Roles in Function, Dysfunction, and Disease

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 366
Author(s):  
Sophia Kelaini ◽  
Celine Chan ◽  
Victoria A Cornelius ◽  
Andriana Margariti
Keyword(s):  
Rna Splicing ◽  
Cellular Localization ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Good Health ◽  
Binding Affinities ◽  
Loss Of Function ◽  
Typical Function ◽  
Transcriptional Alterations

RNA-binding proteins (RBPs) are multi-faceted proteins in the regulation of RNA or its RNA splicing, localisation, stability, and translation. Amassing proof from many recent and dedicated studies reinforces the perception of RBPs exerting control through differing expression levels, cellular localization and post-transcriptional alterations. However, since the regulation of RBPs is reliant on the micro-environment and events like stress response and metabolism, their binding affinities and the resulting RNA-RBP networks may be affected. Therefore, any misregulation and disruption in the features of RNA and its related homeostasis can lead to a number of diseases that include diabetes, cardiovascular disease, and other disorders such as cancer and neurodegenerative diseases. As such, correct regulation of RNA and RBPs is crucial to good health as the effect RBPs exert through loss of function can cause pathogenesis. In this review, we will discuss the significance of RBPs and their typical function and how this can be disrupted in disease.

scholarly journals The QKI-5 and QKI-6 RNA Binding Proteins Regulate the Expression of MicroRNA 7 in Glial Cells

2013 ◽  
Vol 33 (6) ◽  
pp. 1233-1243 ◽  
Author(s):  
Yunling Wang ◽  
Gillian Vogel ◽  
Zhenbao Yu ◽  
Stéphane Richard
Keyword(s):  
Glial Cells ◽  
Rna Splicing ◽  
Cellular Localization ◽  
Binding Proteins ◽  
Rna Binding ◽  
Egf Receptor ◽  
Cell Function ◽  
Rna Binding Proteins ◽  
Glioblastoma Cells ◽  
Egfr Expression

Thequaking(qkI) gene encodes 3 major alternatively spliced isoforms that contain unique sequences at their C termini dictating their cellular localization. QKI-5 is predominantly nuclear, whereas QKI-6 is distributed throughout the cell and QKI-7 is cytoplasmic. The QKI isoforms are sequence-specific RNA binding proteins expressed mainly in glial cells modulating RNA splicing, export, and stability. Herein, we identify a new role for the QKI proteins in the regulation of microRNA (miRNA) processing. We observed that small interfering RNA (siRNA)-mediated QKI depletion of U343 glioblastoma cells leads to a robust increase in miR-7 expression. The processing from primary to mature miR-7 was inhibited in the presence QKI-5 and QKI-6 but not QKI-7, suggesting that the nuclear localization plays an important role in the regulation of miR-7 expression. The primary miR-7-1 was bound by the QKI isoforms in a QKI response element (QRE)-specific manner. We observed that the pri-miR-7-1 RNA was tightly bound to Drosha in the presence of the QKI isoforms, and this association was not observed in siRNA-mediated QKI or Drosha-depleted U343 glioblastoma cells. Moreover, the presence of the QKI isoforms led to an increase presence of pri-miR-7 in nuclear foci, suggesting that pri-miR-7-1 is retained in the nucleus by the QKI isoforms. miR-7 is known to target the epidermal growth factor (EGF) receptor (EGFR) 3′ untranslated region (3′-UTR), and indeed, QKI-deficient U343 cells had reduced EGFR expression and decreased ERK activation in response to EGF. Elevated levels of miR-7 are associated with cell cycle arrest, and it was observed that QKI-deficient U343 that harbor elevated levels of miR-7 exhibited defects in cell proliferation that were partially rescued by the addition of a miR-7 inhibitor. These findings suggest that the QKI isoforms regulate glial cell function and proliferation by regulating the processing of certain miRNAs.

scholarly journals Multiple roles of heterogeneous nuclear ribonucleoprotein K during skeletal muscle cell differentiation

2021 ◽  
Author(s):  
Keisuke Hitachi ◽  
Yuri Kiyofuji ◽  
Masashi Nakatani ◽  
Kunihiro Tsuchida
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Complexes ◽  
Myogenic Differentiation ◽  
Cell Physiology ◽  
Transcriptional Level ◽  
Loss Of Function ◽  
Independent Manner ◽  
Multiple Functions

RNA-binding proteins (RBPs) regulate cell physiology via the formation of ribonucleic-protein complexes with coding and non-coding RNAs. RBPs have multiple functions in the same cells; however, the precise mechanism through which their pleiotropic functions are determined remains unknown. In this study, we revealed the multiple inhibitory functions of hnRNPK for myogenic differentiation. We first identified hnRNPK as a lncRNA Myoparr binding protein. Gain- and loss-of-function experiments showed that hnRNPK repressed the expression of myogenin at the transcriptional level via binding to Myoparr. Moreover, hnRNPK repressed the expression of a set of genes coding for aminoacyl-tRNA synthetases in a Myoparr-independent manner. Mechanistically, hnRNPK regulated the eIF2α/Atf4 pathway, one branch of the intrinsic pathways of the endoplasmic reticulum sensors, in differentiating myoblasts. Thus, our findings demonstrate that hnRNPK plays multiple lncRNA-dependent and -independent roles in the inhibition of myogenic differentiation, indicating that the analysis of lncRNA-binding proteins will be useful for elucidating both the physiological functions of lncRNAs and the multiple functions of RBPs.

scholarly journals Cellular RNA Binding Proteins NS1-BP and hnRNP K Regulate Influenza A Virus RNA Splicing

2013 ◽  
Vol 9 (6) ◽  
pp. e1003460 ◽  
Author(s):  
Pei-Ling Tsai ◽  
Ni-Ting Chiou ◽  
Sharon Kuss ◽  
Adolfo García-Sastre ◽  
Kristen W. Lynch ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Rna Splicing ◽  
Influenza A ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Hnrnp K ◽  
Virus Rna

scholarly journals Trypanosoma brucei RNA Binding Proteins p34 and p37 Mediate NOPP44/46 Cellular Localization via the Exportin 1 Nuclear Export Pathway

2007 ◽  
Vol 6 (12) ◽  
pp. 2206-2213 ◽  
Author(s):  
Kristina Hellman ◽  
Kimberly Prohaska ◽  
Noreen Williams
Keyword(s):  
Amino Acid ◽  
Trypanosoma Brucei ◽  
Nuclear Export ◽  
Cellular Localization ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nuclear Export Signal ◽  
Amino Acid Sequences ◽  
Protein Levels

ABSTRACT We have previously identified and characterized two novel nuclear RNA binding proteins, p34 and p37, which have been shown to interact with a family of nucleolar phosphoproteins, NOPP44/46, in Trypanosoma brucei. These proteins are nearly identical, the major difference being an 18-amino-acid insert in the N terminus of p37. In order to characterize the interaction between p34 and p37 and NOPP44/46, we have utilized an RNA interference (RNAi) cell line that specifically targets p34 and p37. Within these RNAi cells, we detected a disruption of a higher-molecular-weight complex containing NOPP44/46, as well as a dramatic increase in nuclear NOPP44/46 protein levels. We demonstrated that no change occurred in NOPP44/46 mRNA steady-state levels or stability, nor was there a change in cellular protein levels. These results led us to investigate whether p34 and p37 regulate NOPP44/46 cellular localization. Examination of the p34 and p37 amino acid sequences revealed a leucine-rich nuclear export signal, which interacts with the nuclear export factor exportin 1. Immune capture experiments demonstrated that p34, p37, and NOPP44/46 associate with exportin 1. When these experiments were performed with p34/p37 RNAi cells, NOPP44/46 no longer associated with exportin 1. Sequential immune capture experiments demonstrated that p34, p37, NOPP44/46, and exportin 1 exist in a common complex. Inhibiting exportin 1-mediated nuclear export led to an increase in nuclear NOPP44/46 proteins, indicating that they are exported from the nucleus via this pathway. Together, our results demonstrate that p34 and p37 regulate NOPP44/46 cellular localization by facilitating their association with exportin 1.

scholarly journals Binding patterns of RNA-binding proteins to repeat-derived RNA sequences reveal putative functional RNA elements

2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Masahiro Onoguchi ◽  
Chao Zeng ◽  
Ayako Matsumaru ◽  
Michiaki Hamada
Keyword(s):  
Rna Splicing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Noncoding Rnas ◽  
Biological Processes ◽  
Rna Sequences ◽  
Rna Elements ◽  
Long Interspersed Element ◽  
Functional Rna

Abstract Recent reports have revealed that repeat-derived sequences embedded in introns or long noncoding RNAs (lncRNAs) are targets of RNA-binding proteins (RBPs) and contribute to biological processes such as RNA splicing or transcriptional regulation. These findings suggest that repeat-derived RNAs are important as scaffolds of RBPs and functional elements. However, the overall functional sequences of the repeat-derived RNAs are not fully understood. Here, we show the putative functional repeat-derived RNAs by analyzing the binding patterns of RBPs based on ENCODE eCLIP data. We mapped all eCLIP reads to repeat sequences and observed that 10.75 % and 7.04 % of reads on average were enriched (at least 2-fold over control) in the repeats in K562 and HepG2 cells, respectively. Using these data, we predicted functional RNA elements on the sense and antisense strands of long interspersed element 1 (LINE1) sequences. Furthermore, we found several new sets of RBPs on fragments derived from other transposable element (TE) families. Some of these fragments show specific and stable secondary structures and are found to be inserted into the introns of genes or lncRNAs. These results suggest that the repeat-derived RNA sequences are strong candidates for the functional RNA elements of endogenous noncoding RNAs.

scholarly journals RNA-Binding Proteins as Targets to Improve Salt Stress Tolerance in Crops

Agronomy ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 250 ◽  
Author(s):  
Sara Rosa Téllez ◽  
Rodoldphe Kanhonou ◽  
Carlos Castellote Bellés ◽  
Ramón Serrano ◽  
Paula Alepuz ◽  
...  
Keyword(s):  
Salt Stress ◽  
Salt Tolerance ◽  
Sugar Beet ◽  
Rna Splicing ◽  
Yeast Strain ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Crop Improvement ◽  
Salt Toxicity

Salt stress drastically reduce crop productivity. In order to identify genes that could improve crop salt tolerance, we randomly expressed a cDNA library of the halotolerant sugar beet in a sodium-sensitive yeast strain. We identified six sugar beet genes coding for RNA binding proteins (RBP) able to increase the yeast Na+-tolerance. Two of these genes, named Beta vulgaris Salt Tolerant 3 (BvSATO3) and BvU2AF35b, participate in RNA splicing. The other four BvSATO genes (BvSATO1, BvSATO2, BvSATO4 and BvSATO6) are putatively involved in other processes of RNA metabolism. BvU2AF35b improved the growth of a wild type yeast strain under salt stress, and also in mutant backgrounds with impaired splicing, thus confirming that splicing is a target of salt toxicity. To validate the yeast approach, we characterized BvSATO1 in sugar beet and Arabidopsis. BvSATO1 expression was repressed by salt treatment in sugar beet, suggesting that this gene could be a target of salt toxicity. Expression of BvSATO1 in Arabidopsis increased the plant salt tolerance. Our results suggest that not only RNA splicing, but RNA metabolic processes such as such as RNA stability or nonsense-mediated mRNA decay may also be affected by salt stress and could be biotechnological targets for crop improvement.

Comprehensive analysis of differences of N6-methyladenosine RNA methylomes between high-fat-fed and normal mouse livers

Epigenomics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1267-1282 ◽  
Author(s):  
Zupeng Luo ◽  
Zhiwang Zhang ◽  
Lina Tai ◽  
Lifang Zhang ◽  
Zheng Sun ◽  
...  
Keyword(s):  
Fatty Liver ◽  
High Fat Diet ◽  
Rna Splicing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Normal Liver ◽  
Comprehensive Analysis ◽  
Control Group ◽  
High Fat

Aim: To assess the m6A methylome in mouse fatty liver induced by a high-fat diet (HFD). Materials & methods: MeRIP-seq was performed to identify differences in the m6A methylomes between the normal liver and fatty liver induced by an HFD. Results: As compared with the control group, the upmethylated coding genes upon feeding an HFD were primarily enriched in processes associated with lipid metabolism, while genes with downmethylation were enriched in processes associated with metabolism and translation. Furthermore, many RNA-binding proteins that potentially bind to differentially methylated m6A sites were mainly annotated in processes of RNA splicing. Conclusion: These findings suggest that differential m6A methylation may act on functional genes through RNA-binding proteins to regulate the metabolism of lipids in fatty liver disease.

scholarly journals Concentration and localization of co-expressed ELAV/Hu proteins control specificity of mRNA processing

2015 ◽  
pp. MCB.00473-15 ◽  
Author(s):  
Emanuela Zaharieva ◽  
Irmgard U. Haussmann ◽  
Ulrike Bräuer ◽  
Matthias Soller
Keyword(s):  
Cellular Localization ◽  
Binding Proteins ◽  
Target Genes ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Mrna Processing ◽  
Hu Proteins ◽  
Sex Lethal ◽  
Specific Regulation

Neuronally co-expressed ELAV/Hu proteins comprise a family of highly related RNA binding proteins, which bind to very similar cognate sequences. How this redundancy is linked to in vivo function and how gene specific regulation is achieved, has not been clear. Analysis of mutants inDrosophilaELAV/Hu family proteins ELAV, FNE and RBP9, and genetic interactions among them, indicates mostly independent roles in neuronal development and function, but convergence in the regulation of synaptic plasticity. Conversely, ELAV, FNE, RBP9 and human HuR bind ELAV target RNA in vitro with similar affinity. Likewise, all can regulate alternative splicing of ELAV target genes in non-neuronal wing-disc cells and substitute ELAV in eye development with artificially increased expression, but can also substantially restore ELAV's biological functions, when expressed under the control of theelavgene. Furthermore, ELAV related Sex-lethal can regulate ELAV targets and ELAV/Hu proteins can interfere with sexual differentiation. An ancient relationship to Sex-lethal is revealed by gonadal expression of RBP9 providing a maternal failsafe for dosage compensation. Our results indicate that highly related ELAV/Hu RNA binding proteins select targets for mRNA processing based on expression levels and sub-cellular localization, but only minimally by altered RNA binding specificity.

Sign in / Sign up

Export Citation Format

Share Document