rna binding proteins
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2022 ◽  
Vol 23 (2) ◽  
pp. 942
Michele Spiniello ◽  
Mark Scalf ◽  
Amelia Casamassimi ◽  
Ciro Abbondanza ◽  
Lloyd M. Smith

RNA-binding proteins are crucial to the function of coding and non-coding RNAs. The disruption of RNA–protein interactions is involved in many different pathological states. Several computational and experimental strategies have been developed to identify protein binders of selected RNA molecules. Amongst these, ‘in cell’ hybridization methods represent the gold standard in the field because they are designed to reveal the proteins bound to specific RNAs in a cellular context. Here, we compare the technical features of different ‘in cell’ hybridization approaches with a focus on their advantages, limitations, and current and potential future applications.

RNA ◽  
2022 ◽  
pp. rna.079016.121
Chi-Ping Chan ◽  
Dong-Yan Jin

Sensing of pathogen-associated molecular patterns including viral RNA by innate immunity represents the first line of defense against viral infection. In addition to RIG-I-like receptors and NOD-like receptors, several other RNA sensors are known to mediate innate antiviral response in the cytoplasm. Double-stranded RNA-binding protein PACT interacts with prototypic RNA sensor RIG-I to facilitate its recognition of viral RNA and induction of host interferon response, but variations of this theme are seen when the functions of RNA sensors are modulated by other RNA-binding proteins to impinge on antiviral defense, proinflammatory cytokine production and cell death programs. Their discrete and coordinated actions are crucial to protect the host from infection. In this review, we will focus on cytoplasmic RNA sensors with an emphasis on their interplay with RNA-binding partners. Classical sensors such as RIG-I will be briefly reviewed. More attention will be brought to the new insights on how RNA-binding partners of RNA sensors modulate innate RNA sensing and how viruses perturb the functions of RNA-binding partners.

2022 ◽  
Vol 4 (1) ◽  
Warren B Rouse ◽  
Ryan J Andrews ◽  
Nicholas J Booher ◽  
Jibo Wang ◽  
Michael E Woodman ◽  

ABSTRACT In recent years, interest in RNA secondary structure has exploded due to its implications in almost all biological functions and its newly appreciated capacity as a therapeutic agent/target. This surge of interest has driven the development and adaptation of many computational and biochemical methods to discover novel, functional structures across the genome/transcriptome. To further enhance efforts to study RNA secondary structure, we have integrated the functional secondary structure prediction tool ScanFold, into IGV. This allows users to directly perform structure predictions and visualize results—in conjunction with probing data and other annotations—in one program. We illustrate the utility of this new tool by mapping the secondary structural landscape of the human MYC precursor mRNA. We leverage the power of vast ‘omics’ resources by comparing individually predicted structures with published data including: biochemical structure probing, RNA binding proteins, microRNA binding sites, RNA modifications, single nucleotide polymorphisms, and others that allow functional inferences to be made and aid in the discovery of potential drug targets. This new tool offers the RNA community an easy to use tool to find, analyze, and characterize RNA secondary structures in the context of all available data, in order to find those worthy of further analyses.

2022 ◽  
Murat C Kalem ◽  
Harini Subbiah ◽  
Shichen Shen ◽  
Runpu Chen ◽  
Luke Terry ◽  

Protein arginine methylation is a key post-translational modification in eukaryotes that modulates core cellular processes, including translation, morphology, transcription, and RNA fate. However, this has not been explored in Cryptococcus neoformans, a human-pathogenic basidiomycetous encapsulated fungus. We characterized the five protein arginine methyltransferases in C. neoformans and highlight Rmt5 as critical regulator of cryptococcal morphology and virulence. An rmt5∆ mutant was defective in thermotolerance, had a remodeled cell wall, and exhibited enhanced growth in an elevated carbon dioxide atmosphere and in chemically induced hypoxia. We revealed that Rmt5 interacts with post-transcriptional gene regulators, such as RNA-binding proteins and translation factors. Further investigation of the rmt5∆ mutant showed that Rmt5 is critical for the homeostasis of eIF2α and its phosphorylation state following 3-amino-1,2,4-triazole-induced ribosome stalling. RNA sequencing of one rmt5∆ clone revealed stable chromosome 9 aneuploidy that was ameliorated by complementation but did not impact the rmt5∆ phenotype. As a result of these diverse interactions and functions, loss of RMT5 enhanced phagocytosis by murine macrophages and attenuated disease progression in mice. Taken together, our findings link arginine methylation to critical cryptococcal cellular processes that impact pathogenesis, including post-transcriptional gene regulation by RNA- binding proteins.

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 415
Limin Jiang ◽  
Hui Yu ◽  
Scott Ness ◽  
Peng Mao ◽  
Fei Guo ◽  

Somatic mutations are one of the most important factors in tumorigenesis and are the focus of most cancer-sequencing efforts. The co-occurrence of multiple mutations in one tumor has gained increasing attention as a means of identifying cooperating mutations or pathways that contribute to cancer. Using multi-omics, phenotypical, and clinical data from 29,559 cancer subjects and 1747 cancer cell lines covering 78 distinct cancer types, we show that co-mutations are associated with prognosis, drug sensitivity, and disparities in sex, age, and race. Some co-mutation combinations displayed stronger effects than their corresponding single mutations. For example, co-mutation TP53:KRAS in pancreatic adenocarcinoma is significantly associated with disease specific survival (hazard ratio = 2.87, adjusted p-value = 0.0003) and its prognostic predictive power is greater than either TP53 or KRAS as individually mutated genes. Functional analyses revealed that co-mutations with higher prognostic values have higher potential impact and cause greater dysregulation of gene expression. Furthermore, many of the prognostically significant co-mutations caused gains or losses of binding sequences of RNA binding proteins or micro RNAs with known cancer associations. Thus, detailed analyses of co-mutations can identify mechanisms that cooperate in tumorigenesis.

2022 ◽  
Vol 12 (1) ◽  
Claudia Cava ◽  
Alexandros Armaos ◽  
Benjamin Lang ◽  
Gian G. Tartaglia ◽  
Isabella Castiglioni

AbstractBreast cancer is a heterogeneous disease classified into four main subtypes with different clinical outcomes, such as patient survival, prognosis, and relapse. Current genetic tests for the differential diagnosis of BC subtypes showed a poor reproducibility. Therefore, an early and correct diagnosis of molecular subtypes is one of the challenges in the clinic. In the present study, we identified differentially expressed genes, long non-coding RNAs and RNA binding proteins for each BC subtype from a public dataset applying bioinformatics algorithms. In addition, we investigated their interactions and we proposed interacting biomarkers as potential signature specific for each BC subtype. We found a network of only 2 RBPs (RBM20 and PCDH20) and 2 genes (HOXB3 and RASSF7) for luminal A, a network of 21 RBPs and 53 genes for luminal B, a HER2-specific network of 14 RBPs and 30 genes, and a network of 54 RBPs and 302 genes for basal BC. We validated the signature considering their expression levels on an independent dataset evaluating their ability to classify the different molecular subtypes with a machine learning approach. Overall, we achieved good performances of classification with an accuracy >0.80. In addition, we found some interesting novel prognostic biomarkers such as RASSF7 for luminal A, DCTPP1 for luminal B, DHRS11, KLC3, NAGS, and TMEM98 for HER2, and ABHD14A and ADSSL1 for basal. The findings could provide preliminary evidence to identify putative new prognostic biomarkers and therapeutic targets for individual breast cancer subtypes.

2022 ◽  
Kai-Ren Luo ◽  
Nien-Chen Huang ◽  
Yu-Hsin Chang ◽  
Tien-Shin Yu

Abstract Plants selectively transport mobile mRNAs through intercellular pores, plasmodesmata (PD), to distribute spatial information for synchronizing meristematic differentiation with environmental dynamics. However, how plants recognize and deliver mobile mRNAs to PD remains unknown. Here, by using RNA-live cell imaging, we show that mobile mRNAs hitchhike on organelle trafficking to transport to PD. Perturbed cytoskeleton organization or organelle trafficking severely disrupts the subcellular distribution of mobile mRNAs. We further show that Arabidopsis rotamase cyclophilins (ROCs), which are organelle-localized RNA-binding proteins (RBPs), specifically bind mobile mRNAs on the surface of organelles to direct PD-targeting. Arabidopsis roc quadruple mutants showed reduced in PD-targeting of mobile mRNAs, along with phenotype alterations. ROCs can move intercellularly and form RNA-protein complexes in phloem, suggesting the roles of ROCs in delivery of mobile mRNAs through PD. Our results highlight that an RBP-mediated hitchhiking system is purposely recruited to orient plant-mobile mRNAs to PD for intercellular transport.

2022 ◽  
Zi‐Ting Yao ◽  
Yan‐Ming Yang ◽  
Miao‐Miao Sun ◽  
Yan He ◽  
Long Liao ◽  

Gut ◽  
2022 ◽  
pp. gutjnl-2021-325109
Jonas Nørskov Søndergaard ◽  
Christian Sommerauer ◽  
Ionut Atanasoai ◽  
Laura C Hinte ◽  
Keyi Geng ◽  

ObjectiveTo better comprehend transcriptional phenotypes of cancer cells, we globally characterised RNA-binding proteins (RBPs) to identify altered RNAs, including long non-coding RNAs (lncRNAs).DesignTo unravel RBP-lncRNA interactions in cancer, we curated a list of ~2300 highly expressed RBPs in human cells, tested effects of RBPs and lncRNAs on patient survival in multiple cohorts, altered expression levels, integrated various sequencing, molecular and cell-based data.ResultsHigh expression of RBPs negatively affected patient survival in 21 cancer types, especially hepatocellular carcinoma (HCC). After knockdown of the top 10 upregulated RBPs and subsequent transcriptome analysis, we identified 88 differentially expressed lncRNAs, including 34 novel transcripts. CRISPRa-mediated overexpression of four lncRNAs had major effects on the HCC cell phenotype and transcriptome. Further investigation of four RBP-lncRNA pairs revealed involvement in distinct regulatory processes. The most noticeable RBP-lncRNA connection affected lipid metabolism, whereby the non-canonical RBP CCT3 regulated LINC00326 in a chaperonin-independent manner. Perturbation of the CCT3-LINC00326 regulatory network led to decreased lipid accumulation and increased lipid degradation in cellulo as well as diminished tumour growth in vivo.ConclusionsWe revealed that RBP gene expression is perturbed in HCC and identified that RBPs exerted additional functions beyond their tasks under normal physiological conditions, which can be stimulated or intensified via lncRNAs and affected tumour growth.

2022 ◽  
Vol 5 (4) ◽  
pp. e202101252
Belén Chaves-Arquero ◽  
Santiago Martínez-Lumbreras ◽  
Sergio Camero ◽  
Clara M Santiveri ◽  
Yasmina Mirassou ◽  

Heterodimerization of RNA binding proteins Nrd1 and Nab3 is essential to communicate the RNA recognition in the nascent transcript with the Nrd1 recognition of the Ser5-phosphorylated Rbp1 C-terminal domain in RNA polymerase II. The structure of a Nrd1–Nab3 chimera reveals the basis of heterodimerization, filling a missing gap in knowledge of this system. The free form of the Nrd1 interaction domain of Nab3 (NRID) forms a multi-state three-helix bundle that is clamped in a single conformation upon complex formation with the Nab3 interaction domain of Nrd1 (NAID). The latter domain forms two long helices that wrap around NRID, resulting in an extensive protein–protein interface that would explain the highly favorable free energy of heterodimerization. Mutagenesis of some conserved hydrophobic residues involved in the heterodimerization leads to temperature-sensitive phenotypes, revealing the importance of this interaction in yeast cell fitness. The Nrd1–Nab3 structure resembles the previously reported Rna14/Rna15 heterodimer structure, which is part of the poly(A)-dependent termination pathway, suggesting that both machineries use similar structural solutions despite they share little sequence homology and are potentially evolutionary divergent.

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