scholarly journals RBP2GO: a comprehensive pan-species database on RNA-binding proteins, their interactions and functions

2020 ◽  
Vol 49 (D1) ◽  
pp. D425-D436 ◽  
Author(s):  
Maiwen Caudron-Herger ◽  
Ralf E Jansen ◽  
Elsa Wassmer ◽  
Sven Diederichs

Abstract RNA–protein complexes have emerged as central players in numerous key cellular processes with significant relevance in health and disease. To further deepen our knowledge of RNA-binding proteins (RBPs), multiple proteome-wide strategies have been developed to identify RBPs in different species leading to a large number of studies contributing experimentally identified as well as predicted RBP candidate catalogs. However, the rapid evolution of the field led to an accumulation of isolated datasets, hampering the access and comparison of their valuable content. Moreover, tools to link RBPs to cellular pathways and functions were lacking. Here, to facilitate the efficient screening of the RBP resources, we provide RBP2GO (https://RBP2GO.DKFZ.de), a comprehensive database of all currently available proteome-wide datasets for RBPs across 13 species from 53 studies including 105 datasets identifying altogether 22 552 RBP candidates. These are combined with the information on RBP interaction partners and on the related biological processes, molecular functions and cellular compartments. RBP2GO offers a user-friendly web interface with an RBP scoring system and powerful advanced search tools allowing forward and reverse searches connecting functions and RBPs to stimulate new research directions.

2019 ◽  
Vol 14 (7) ◽  
pp. 621-627 ◽  
Author(s):  
Youhuang Bai ◽  
Xiaozhuan Dai ◽  
Tiantian Ye ◽  
Peijing Zhang ◽  
Xu Yan ◽  
...  

Background: Long noncoding RNAs (lncRNAs) are endogenous noncoding RNAs, arbitrarily longer than 200 nucleotides, that play critical roles in diverse biological processes. LncRNAs exist in different genomes ranging from animals to plants. Objective: PlncRNADB is a searchable database of lncRNA sequences and annotation in plants. Methods: We built a pipeline for lncRNA prediction in plants, providing a convenient utility for users to quickly distinguish potential noncoding RNAs from protein-coding transcripts. Results: More than five thousand lncRNAs are collected from four plant species (Arabidopsis thaliana, Arabidopsis lyrata, Populus trichocarpa and Zea mays) in PlncRNADB. Moreover, our database provides the relationship between lncRNAs and various RNA-binding proteins (RBPs), which can be displayed through a user-friendly web interface. Conclusion: PlncRNADB can serve as a reference database to investigate the lncRNAs and their interaction with RNA-binding proteins in plants. The PlncRNADB is freely available at http://bis.zju.edu.cn/PlncRNADB/.


2021 ◽  
Author(s):  
Keisuke Hitachi ◽  
Yuri Kiyofuji ◽  
Masashi Nakatani ◽  
Kunihiro Tsuchida

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.


2020 ◽  
Vol 21 (18) ◽  
pp. 6835
Author(s):  
Jonas Weiße ◽  
Julia Rosemann ◽  
Vanessa Krauspe ◽  
Matthias Kappler ◽  
Alexander W. Eckert ◽  
...  

Nearly 7.5% of all human protein-coding genes have been assigned to the class of RNA-binding proteins (RBPs), and over the past decade, RBPs have been increasingly recognized as important regulators of molecular and cellular homeostasis. RBPs regulate the post-transcriptional processing of their target RNAs, i.e., alternative splicing, polyadenylation, stability and turnover, localization, or translation as well as editing and chemical modification, thereby tuning gene expression programs of diverse cellular processes such as cell survival and malignant spread. Importantly, metastases are the major cause of cancer-associated deaths in general, and particularly in oral cancers, which account for 2% of the global cancer mortality. However, the roles and architecture of RBPs and RBP-controlled expression networks during the diverse steps of the metastatic cascade are only incompletely understood. In this review, we will offer a brief overview about RBPs and their general contribution to post-transcriptional regulation of gene expression. Subsequently, we will highlight selected examples of RBPs that have been shown to play a role in oral cancer cell migration, invasion, and metastasis. Last but not least, we will present targeting strategies that have been developed to interfere with the function of some of these RBPs.


2020 ◽  
Vol 21 (8) ◽  
pp. 2969 ◽  
Author(s):  
Katharina Jonas ◽  
George A. Calin ◽  
Martin Pichler

The majority of the genome is transcribed into pieces of non-(protein) coding RNA, among which long non-coding RNAs (lncRNAs) constitute a large group of particularly versatile molecules that govern basic cellular processes including transcription, splicing, RNA stability, and translation. The frequent deregulation of numerous lncRNAs in cancer is known to contribute to virtually all hallmarks of cancer. An important regulatory mechanism of lncRNAs is the post-transcriptional regulation mediated by RNA-binding proteins (RBPs). So far, however, only a small number of known cancer-associated lncRNAs have been found to be regulated by the interaction with RBPs like human antigen R (HuR), ARE/poly(U)-binding/degradation factor 1 (AUF1), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and tristetraprolin (TTP). These RBPs regulate, by various means, two aspects in particular, namely the stability and the localization of lncRNAs. Importantly, these RBPs themselves are commonly deregulated in cancer and might thus play a major role in the deregulation of cancer-related lncRNAs. There are, however, still many open questions, for example regarding the context specificity of these regulatory mechanisms that, in part, is based on the synergistic or competitive interaction between different RBPs. There is also a lack of knowledge on how RBPs facilitate the transport of lncRNAs between different cellular compartments.


2021 ◽  
Author(s):  
Helisa H Wippel ◽  
Mariana Fioramonte ◽  
Juan D Chavez ◽  
James E Bruce

RNA-binding proteins (RBPs) have conserved domains and consensus sequences that interact with RNAs and other proteins forming ribonucleoprotein (RNP) complexes. RNPs are involved in the regulation of several cellular processes,...


2020 ◽  
Vol 48 (11) ◽  
pp. 5859-5872
Author(s):  
Danielle A Adekunle ◽  
Eric T Wang

Abstract Subcellular organization of RNAs and proteins is critical for cell function, but we still lack global maps and conceptual frameworks for how these molecules are localized in cells and tissues. Here, we introduce ATLAS-Seq, which generates transcriptomes and proteomes from detergent-free tissue lysates fractionated across a sucrose gradient. Proteomic analysis of fractions confirmed separation of subcellular compartments. Unexpectedly, RNAs tended to co-sediment with other RNAs in similar protein complexes, cellular compartments, or with similar biological functions. With the exception of those encoding secreted proteins, most RNAs sedimented differently than their encoded protein counterparts. To identify RNA binding proteins potentially driving these patterns, we correlated their sedimentation profiles to all RNAs, confirming known interactions and predicting new associations. Hundreds of alternative RNA isoforms exhibited distinct sedimentation patterns across the gradient, despite sharing most of their coding sequence. These observations suggest that transcriptomes can be organized into networks of co-segregating mRNAs encoding functionally related proteins and provide insights into the establishment and maintenance of subcellular organization.


2019 ◽  
Vol 60 (9) ◽  
pp. 1939-1952 ◽  
Author(s):  
Wil Prall ◽  
Bishwas Sharma ◽  
Brian D Gregory

Abstract Plants have developed sophisticated mechanisms to compensate and respond to ever-changing environmental conditions. Research focus in this area has recently shifted towards understanding the post-transcriptional mechanisms that contribute to RNA transcript maturation, abundance and function as key regulatory steps in allowing plants to properly react and adapt to these never-ending shifts in their environments. At the center of these regulatory mechanisms are RNA-binding proteins (RBPs), the functional mediators of all post-transcriptional processes. In plants, RBPs are becoming increasingly appreciated as the critical modulators of core cellular processes during development and in response to environmental stimuli. With the majority of research on RBPs and their functions historically in prokaryotic and mammalian systems, it has more recently been unveiled that plants have expanded families of conserved and novel RBPs compared with their eukaryotic counterparts. To better understand the scope of RBPs in plants, we present past and current literature detailing specific roles of RBPs during stress response, development and other fundamental transition periods. In this review, we highlight examples of complex regulation coordinated by RBPs with a focus on the diverse mechanisms of plant RBPs and the unique processes they regulate. Additionally, we discuss the importance for additional research into understanding global interactions of RBPs on a systems and network-scale, with genome mining and annotation providing valuable insight for potential uses in improving crop plants in order to maintain high-level production in this era of global climate change.


Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2270
Author(s):  
Ronja Weissinger ◽  
Lisa Heinold ◽  
Saira Akram ◽  
Ralf-Peter Jansen ◽  
Orit Hermesh

Multiple cellular functions are controlled by the interaction of RNAs and proteins. Together with the RNAs they control, RNA interacting proteins form RNA protein complexes, which are considered to serve as the true regulatory units for post-transcriptional gene expression. To understand how RNAs are modified, transported, and regulated therefore requires specific knowledge of their interaction partners. To this end, multiple techniques have been developed to characterize the interaction between RNAs and proteins. In this review, we briefly summarize the common methods to study RNA–protein interaction including crosslinking and immunoprecipitation (CLIP), and aptamer- or antisense oligonucleotide-based RNA affinity purification. Following this, we focus on in vivo proximity labeling to study RNA–protein interactions. In proximity labeling, a labeling enzyme like ascorbate peroxidase or biotin ligase is targeted to specific RNAs, RNA-binding proteins, or even cellular compartments and uses biotin to label the proteins and RNAs in its vicinity. The tagged molecules are then enriched and analyzed by mass spectrometry or RNA-Seq. We highlight the latest studies that exemplify the strength of this approach for the characterization of RNA protein complexes and distribution of RNAs in vivo.


2022 ◽  
Author(s):  
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.


2019 ◽  
Author(s):  
Jian-You Liao ◽  
Bing Yang ◽  
Yu-Chan Zhang ◽  
Xiao-Juan Wang ◽  
Yushan Ye ◽  
...  

ABSTRACTRNA binding proteins (RBPs) are a large protein family that plays important roles at almost all levels of gene regulation through interacting with RNAs, and contributes to numerous biological processes. However, the complete list of eukaryotic RBPs including human is still unavailable. In this study, we systematically identified RBPs in 162 eukaryotic species based on both computational analysis of RNA binding domains (RBDs) and large-scale RNA binding proteomic (RBPome) data, and established a comprehensive eukaryotic RBP database, EuRBPDB (http://EuRBPDB.syshospital.org:8081). We identified a total of 311,571 RBPs with RBDs and 3,639 non-canonical RBPs without known RBDs. EuRBPDB provides detailed annotations for each RBP, including basic information and functional annotation. Moreover, we systematically investigated RBPs in the context of cancer biology based on published literatures and large-scale omics data. To facilitate the exploration of the clinical relevance of RBPs, we additionally designed a cancer web interface to systematically and interactively display the biological features of RBPs in various types of cancers. EuRBPDB has a user-friendly web interface with browse and search functions, as well as data downloading function. We expect that EuRBPDB will be a widely-used resource and platform for the RNA biology community.


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