scholarly journals Z‐band and M‐band titin splicing and regulation by RNA binding motif 20 in striated muscles

2018 ◽  
Vol 119 (12) ◽  
pp. 9986-9996 ◽  
Author(s):  
Zhilong Chen ◽  
Rexiati Maimaiti ◽  
Chaoqun Zhu ◽  
Hanfang Cai ◽  
Allysa Stern ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Motif ◽  
Striated Muscles

scholarly journals The Combined Human Genotype of Truncating TTN and RBM20 Mutations Is Associated with Severe and Early Onset of Dilated Cardiomyopathy

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 883
Author(s):  
Anna Gaertner ◽  
Julia Bloebaum ◽  
Andreas Brodehl ◽  
Baerbel Klauke ◽  
Katharina Sielemann ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Early Onset ◽  
Target Genes ◽  
Frameshift Mutation ◽  
Rna Binding ◽  
Splicing Factor ◽  
Binding Motif ◽  
Rich Domain ◽  
Generation Sequencing

A major cause of heart failure is cardiomyopathies, with dilated cardiomyopathy (DCM) as the most common form. Over 40 genes are linked to DCM, among them TTN and RBM20. Next Generation Sequencing in clinical DCM cohorts revealed truncating variants in TTN (TTNtv), accounting for up to 25% of familial DCM cases. Mutations in the cardiac splicing factor RNA binding motif protein 20 (RBM20) are also known to be associated with severe cardiomyopathies. TTN is one of the major RBM20 splicing targets. Most of the pathogenic RBM20 mutations are localized in the highly conserved arginine serine rich domain (RS), leading to a cytoplasmic mislocalization of mutant RBM20. Here, we present a patient with an early onset DCM carrying a combination of (likely) pathogenic TTN and RBM20 mutations. We show that the splicing of RBM20 target genes is affected in the mutation carrier. Furthermore, we reveal RBM20 haploinsufficiency presumably caused by the frameshift mutation in RBM20.

scholarly journals RBMX suppresses tumorigenicity and progression of bladder cancer by interacting with the hnRNP A1 protein to regulate PKM alternative splicing

Oncogene ◽  
2021 ◽  
Author(s):  
Qiuxia Yan ◽  
Peng Zeng ◽  
Xiuqin Zhou ◽  
Xiaoying Zhao ◽  
Runqiang Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Alternative Splicing ◽  
Rna Binding ◽  
Aerobic Glycolysis ◽  
Histological Grade ◽  
Migration And Invasion ◽  
Binding Motif ◽  
Hnrnp A1

AbstractThe prognosis for patients with metastatic bladder cancer (BCa) is poor, and it is not improved by current treatments. RNA-binding motif protein X-linked (RBMX) are involved in the regulation of the malignant progression of various tumors. However, the role of RBMX in BCa tumorigenicity and progression remains unclear. In this study, we found that RBMX was significantly downregulated in BCa tissues, especially in muscle-invasive BCa tissues. RBMX expression was negatively correlated with tumor stage, histological grade and poor patient prognosis. Functional assays demonstrated that RBMX inhibited BCa cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth and metastasis in vivo. Mechanistic investigations revealed that hnRNP A1 was an RBMX-binding protein. RBMX competitively inhibited the combination of the RGG motif in hnRNP A1 and the sequences flanking PKM exon 9, leading to the formation of lower PKM2 and higher PKM1 levels, which attenuated the tumorigenicity and progression of BCa. Moreover, RBMX inhibited aerobic glycolysis through hnRNP A1-dependent PKM alternative splicing and counteracted the PKM2 overexpression-induced aggressive phenotype of the BCa cells. In conclusion, our findings indicate that RBMX suppresses BCa tumorigenicity and progression via an hnRNP A1-mediated PKM alternative splicing mechanism. RBMX may serve as a novel prognostic biomarker for clinical intervention in BCa.

scholarly journals Podocalyxin-like and RNA-binding motif protein 3 are prognostic biomarkers in urothelial bladder cancer: a validatory study

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Karolina Boman ◽  
Gustav Andersson ◽  
Christoffer Wennersten ◽  
Björn Nodin ◽  
Göran Ahlgren ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Rna Binding ◽  
Prognostic Biomarkers ◽  
Binding Motif ◽  
Urothelial Bladder Cancer ◽  
Urothelial Bladder

scholarly journals A novel member of the SAF (scaffold attachment factor)-box protein family inhibits gene expression and induces apoptosis

2007 ◽  
Vol 407 (3) ◽  
pp. 355-362 ◽  
Author(s):  
Ching Wan Chan ◽  
Youn-Bok Lee ◽  
James Uney ◽  
Andrea Flynn ◽  
Jonathan H. Tobias ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Chromatin Condensation ◽  
Inhibitory Effect ◽  
Binding Motif ◽  
Inhibitory Effects ◽  
Cytochrome C Release ◽  
Interacting Protein ◽  
Induced Apoptosis ◽  
Attachment Factor

The SLTM [SAF (scaffold attachment factor)-like transcription modulator] protein contains a SAF-box DNA-binding motif and an RNA-binding domain, and shares an overall identity of 34% with SAFB1 {scaffold attachment factor-B1; also known as SAF-B (scaffold attachment factor B), HET [heat-shock protein 27 ERE (oestrogen response element) and TATA-box-binding protein] or HAP (heterogeneous nuclear ribonucleoprotein A1-interacting protein)}. Here, we show that SLTM is localized to the cell nucleus, but excluded from nucleoli, and to a large extent it co-localizes with SAFB1. In the nucleus, SLTM has a punctate distribution and it does not co-localize with SR (serine/arginine) proteins. Overexpression of SAFB1 has been shown to exert a number of inhibitory effects, including suppression of oestrogen signalling. Although SLTM also suppressed the ability of oestrogen to activate a reporter gene in MCF-7 breast-cancer cells, inhibition of a constitutively active β-galactosidase gene suggested that this was primarily the consequence of a generalized inhibitory effect on transcription. Measurement of RNA synthesis, which showed a particularly marked inhibition of [3H]uridine incorporation into mRNA, supported this conclusion. In addition, analysis of cell-cycle parameters, chromatin condensation and cytochrome c release showed that SLTM induced apoptosis in a range of cultured cell lines. Thus the inhibitory effects of SLTM on gene expression appear to result from generalized down-regulation of mRNA synthesis and initiation of apoptosis consequent upon overexpressing the protein. While indicating a crucial role for SLTM in cellular function, these results also emphasize the need for caution when interpreting phenotypic changes associated with manipulation of protein expression levels.

Molecular dissection of a genome defense pathway in Neurospora crassa

2015 ◽  
Author(s):  
◽  
Erin C. Boone
Keyword(s):  
Neurospora Crassa ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nuclear Periphery ◽  
Bimolecular Fluorescence Complementation ◽  
Proper Function ◽  
Rnai Pathway ◽  
Binding Motif ◽  
Perinuclear Region ◽  
A Genome

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Meiotic silencing by unpaired DNA (MSUD) is an RNA interference (RNAi) pathway in Neurospora crassa that detects genes without a homologous partner and silences them for the duration of sexual development. In this study, we have further elucidated the function of known MSUD proteins, identified novel proteins that are required for MSUD, and demonstrated the conservation of RNAi-related processes at the nuclear periphery. We began by showing SAD-2 is crucial for the localization of other MSUD proteins in the perinuclear region. These data suggest that SAD-2 works as a scaffold protein and that proper function of MSUD, like other germline RNAi-like systems, is reliant on the presence of silencing proteins in the perinuclear region. An MSUD suppression assay identified two novel MSUD proteins, SAD-Y and SAD-B'. Even though SAD-Y and its homologs contain a conserved putative RNA- binding motif, they have yet to be assigned to a biochemical pathway. Our work here has linked silencing to SAD-Y-like proteins. SAD-Y has been shown to interact with other MSUD factors in both the nucleus and at the nuclear periphery. SAD-B's homolog has been found in the nuage, an epicenter for RNA-binding proteins involved in post-transcriptional regulation for Drosophila germline cells. SAD-B interacts with core MSUD proteins and has an especially intimate association with SMS-2, which requires it for localization. Furthermore, bimolecular fluorescence complementation (BiFC) revealed that SAD-B' interacts with a Golgi retrograde transport protein and an autophagy marker protein, suggesting the importance of the endomembrane system in this RNAi process.

scholarly journals Comprehensive analysis of RNA binding motif protein 3 (RBM3) in non‐small cell lung cancer

2020 ◽  
Vol 9 (15) ◽  
pp. 5609-5619 ◽  
Author(s):  
Annette Salomonsson ◽  
Patrick Micke ◽  
Johanna S. M. Mattsson ◽  
Linnea La Fleur ◽  
Johan Isaksson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Rna Binding ◽  
Comprehensive Analysis ◽  
Small Cell ◽  
Binding Motif ◽  
Small Cell Lung

scholarly journals Translational induction of ATF4 during integrated stress response requires noncanonical initiation factors eIF2D and DENR

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Deepika Vasudevan ◽  
Sarah D. Neuman ◽  
Amy Yang ◽  
Lea Lough ◽  
Brian Brown ◽  
...  
Keyword(s):  
Stress Response ◽  
Er Stress ◽  
Stress Responses ◽  
Rna Binding ◽  
Open Reading Frames ◽  
Binding Motif ◽  
Integrated Stress Response ◽  
Developmental Defects ◽  
Initiation Factors

Abstract The Integrated Stress Response (ISR) helps metazoan cells adapt to cellular stress by limiting the availability of initiator methionyl-tRNA for translation. Such limiting conditions paradoxically stimulate the translation of ATF4 mRNA through a regulatory 5′ leader sequence with multiple upstream Open Reading Frames (uORFs), thereby activating stress-responsive gene expression. Here, we report the identification of two critical regulators of such ATF4 induction, the noncanonical initiation factors eIF2D and DENR. Loss of eIF2D and DENR in Drosophila results in increased vulnerability to amino acid deprivation, susceptibility to retinal degeneration caused by endoplasmic reticulum (ER) stress, and developmental defects similar to ATF4 mutants. eIF2D requires its RNA-binding motif for regulation of 5′ leader-mediated ATF4 translation. Consistently, eIF2D and DENR deficient human cells show impaired ATF4 protein induction in response to ER stress. Altogether, our findings indicate that eIF2D and DENR are critical mediators of ATF4 translational induction and stress responses in vivo.

scholarly journals RNA-binding protein 39: a promising therapeutic target for cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Caipeng Xu ◽  
Xiaohua Chen ◽  
Xuetian Zhang ◽  
Dapeng Zhao ◽  
Zhihui Dou ◽  
...  
Keyword(s):  
Clinical Application ◽  
Rna Binding ◽  
Drug Research ◽  
Protein Translation ◽  
Vital Role ◽  
Binding Motif ◽  
Promising Therapeutic Target ◽  
Key Factor ◽  
Mrna And Protein Expression ◽  
Development Prospects

AbstractRNA-binding motif protein 39 (RBM39), as a key factor in tumor-targeted mRNA and protein expression, not only plays a vital role in tumorigenesis, but also has broad development prospects in clinical treatment and drug research. Moreover, since RBM39 was identified as a target of sulfonamides, it has played a key role in the emerging field of molecule drug development. Hence, it is of great significance to study the interaction between RBM39 and tumors and the clinical application of drug-targeted therapy. In this paper, we describe the possible multi-level regulation of RBM39, including gene transcription, protein translation, and alternative splicing. Importantly, the molecular function of RBM39 as an important splicing factor in most common tumors is systematically outlined. Furthermore, we briefly introduce RBM39’s tumor-targeted drug research and its clinical application, hoping to give reference significance for the molecular mechanism of RBM39 in tumors, and provide reliable ideas for in-depth research for future therapeutic strategies.

scholarly journals Expression of RNA-binding motif 10 is associated with advanced tumor stage and malignant behaviors of lung adenocarcinoma cancer cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769174 ◽  
Author(s):  
Guofang Guan ◽  
Ranwei Li ◽  
Wenfang Tang ◽  
Tiecheng Liu ◽  
Zhenzhong Su ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Messenger Rna ◽  
Rna Binding ◽  
Tumor Stage ◽  
Receptor Interaction ◽  
Binding Motif ◽  
Advanced Tumor Stage ◽  
Complementary Dna ◽  
Advanced Tumor ◽  
Lung Adenocarcinoma Cancer

This study assessed RNA-binding motif 10 expression in lung adenocarcinoma tissues and examined the role and mechanism of RNA-binding motif 10 in the regulation of lung adenocarcinoma malignancy. Lung adenocarcinoma and corresponding adjacent non-tumor lung tissues from 41 patients were subjected to reverse transcription-polymerase chain reaction and Western blot assessment to detect RNA-binding motif 10 expression. Recombinant lentivirus carrying RNA-binding motif 10 complementary DNA was used to infect lung adenocarcinoma cell lines, A549 and H1299 cells. Complementary DNA microarray was used to profile RNA-binding motif 10–regulated genes. Levels of RNA-binding motif 10 messenger RNA and protein were significantly lower in lung adenocarcinoma tissues than those in paired non-tumor tissues (p < 0.001). Reduced RNA-binding motif 10 expression was found to be associated with an advanced tumor stage. RNA-binding motif 10 overexpression inhibited viability and colony formation capacity of lung adenocarcinoma cell lines and induced cell-cycle arrest at G0/G1 phase in A549 cells and at S phase in H1299 cells. Complementary DNA microarray analysis identified 304 upregulated and 386 downregulated genes induced by RNA-binding motif 10 overexpression, which may be involved in cancer, focal adhesion, peroxisome proliferator-activated receptor–regulated gene pathway, cytokine–cytokine receptor interaction, mitogen-activated protein kinase signaling, complement and coagulation cascades, platelet amyloid precursor protein pathway, extracellular matrix-receptor interaction, and small cell lung cancer–related genes. Expression of FGF2, EGFR, WNT5A, NF-κB, and RAP1A was downregulated, whereas expression of AKT2, BIRC3, and JUN was upregulated. RNA-binding motif 10 messenger RNA and protein were reduced in lung adenocarcinoma tissues, and RNA-binding motif 10 overexpression inhibited lung adenocarcinoma cancer cell malignant behavior in vitro. Molecularly, RNA-binding motif 10 regulates many gene pathways involving in the tumor development or progression.

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