scholarly journals The biological function of m6A reader YTHDF2 and its role in human disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jin-yan Wang ◽  
Ai-qing Lu

AbstractN6-methyladenosine (m6A) modification is a dynamic and reversible post-transcriptional modification and the most prevalent internal RNA modification in eukaryotic cells. YT521-B homology domain family 2 (YTHDF2) is a member of m6A “readers” and its role in human diseases remains unclear. Accumulating evidence suggests that YTHDF2 is greatly implicated in many aspects of human cancers and non-cancers through various mechanisms. YTHDF2 takes a great part in multiple biological processes, such as migration, invasion, metastasis, proliferation, apoptosis, cell cycle, cell viability, cell adhesion, differentiation and inflammation, in both human cancers and non-cancers. Additionally, YTHDF2 influences various aspects of RNA metabolism, including mRNA decay and pre-ribosomal RNA (pre-rRNA) processing. Moreover, emerging researches indicate that YTHDF2 predicts the prognosis of different cancers. Herein, we focus on concluding YTHDF2-associated mechanisms and potential biological functions in kinds of cancers and non-cancers, and its prospects as a prognostic biomarker.

2010 ◽  
Vol 1 (5-6) ◽  
pp. 411-422 ◽  
Author(s):  
André Voelzmann ◽  
Reinhard Bauer

AbstractThe ceramide synthase (CerS) gene family comprises a group of highly conserved transmembrane proteins, which are found in all studied eukaryotes. The key feature of the CerS proteins is their role in ceramide synthase activity. Therefore, their original name ‘longevity assurance gene (Lass) homologs’, after the founding member, the yeast longevity assurance gene lag1, was altered to ‘CerS’. All CerS have high sequence similarity in a domain called LAG1 motif and a subset of CerS proteins is predicted to contain a Homeobox (Hox) domain. These domains could be the key to the multiple roles CerS have. CerS proteins play a role in diverse biological processes such as proliferation, differentiation, apoptosis, stress response, cancer, and neurodegeneration. In this review, we focus on CerS structure and biological function with emphasis of biological functions in the widely used model systems Caenorhabditis elegans and Drosophila melanogaster. Also, we focus on the accumulating data suggesting a role for CerS in lipid homeostasis.


Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Fulei Nie ◽  
Pengmian Feng ◽  
Xiaoming Song ◽  
Meng Wu ◽  
Qiang Tang ◽  
...  

Abstract RNA modifications are involved in various kinds of cellular biological processes. Accumulated evidences have demonstrated that the functions of RNA modifications are determined by the effectors that can catalyze, recognize and remove RNA modifications. They are called ‘writers’, ‘readers’ and ‘erasers’. The identification of RNA modification effectors will be helpful for understanding the regulatory mechanisms and biological functions of RNA modifications. In this work, we developed a database called RNAWRE that specially deposits RNA modification effectors. The current version of RNAWRE stored 2045 manually curated writers, readers and erasers for the six major kinds of RNA modifications, namely Cap, m1A, m6A, m5C, ψ and Poly A. The main modules of RNAWRE not only allow browsing and downloading the RNA modification effectors but also support the BLAST search of the potential RNA modification effectors in other species. We hope that RNAWRE will be helpful for the researches on RNA modifications. Database URL: http://rnawre.bio2db.com


2020 ◽  
Vol 49 (D1) ◽  
pp. D134-D143
Author(s):  
Yujiao Tang ◽  
Kunqi Chen ◽  
Bowen Song ◽  
Jiongming Ma ◽  
Xiangyu Wu ◽  
...  

Abstract N 6-Methyladenosine (m6A) is the most prevalent RNA modification on mRNAs and lncRNAs. It plays a pivotal role during various biological processes and disease pathogenesis. We present here a comprehensive knowledgebase, m6A-Atlas, for unraveling the m6A epitranscriptome. Compared to existing databases, m6A-Atlas features a high-confidence collection of 442 162 reliable m6A sites identified from seven base-resolution technologies and the quantitative (rather than binary) epitranscriptome profiles estimated from 1363 high-throughput sequencing samples. It also offers novel features, such as; the conservation of m6A sites among seven vertebrate species (including human, mouse and chimp), the m6A epitranscriptomes of 10 virus species (including HIV, KSHV and DENV), the putative biological functions of individual m6A sites predicted from epitranscriptome data, and the potential pathogenesis of m6A sites inferred from disease-associated genetic mutations that can directly destroy m6A directing sequence motifs. A user-friendly graphical user interface was constructed to support the query, visualization and sharing of the m6A epitranscriptomes annotated with sites specifying their interaction with post-transcriptional machinery (RBP-binding, microRNA interaction and splicing sites) and interactively display the landscape of multiple RNA modifications. These resources provide fresh opportunities for unraveling the m6A epitranscriptomes. m6A-Atlas is freely accessible at: www.xjtlu.edu.cn/biologicalsciences/atlas.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Bin Xu ◽  
Jie Mei ◽  
Wei Ji ◽  
Zheng Bian ◽  
Jiantong Jiao ◽  
...  

Abstract Long noncoding RNAs (lncRNAs) are composed of > 200 nucleotides; they lack the ability to encode proteins but play important roles in a variety of human tumors. A large number of studies have shown that dysregulated expression of lncRNAs is related to tumor oncogenesis and progression. Emerging evidence shows that SNHG3 is a novel oncogenic lncRNA that is abnormally expressed in various tumors, including osteosarcoma, liver cancer, lung cancer, etc. SNHG3 primarily competes as a competitive endogenous RNA (ceRNA) that targets tumor suppressor microRNAs (miRNAs) and ceRNA mechanisms that regulate biological processes of tumors. In addition, abnormal expression of SNHG3 is significantly correlated with patient clinical features. Upregulation of SNHG3 contributes to biological functions, including tumor cell proliferation, migration, invasion and EMT. Therefore, SNHG3 may represent a potential diagnostic and prognostic biomarker, as well as a novel therapeutic target.


2020 ◽  
Vol 26 ◽  
Author(s):  
Pengmian Feng ◽  
Lijing Feng ◽  
Chaohui Tang

Background and Purpose: N 6 -methyladenosine (m6A) plays critical roles in a broad set of biological processes. Knowledge about the precise location of m6A site in the transcriptome is vital for deciphering its biological functions. Although experimental techniques have made substantial contributions to identify m6A, they are still labor intensive and time consuming. As good complements to experimental methods, in the past few years, a series of computational approaches have been proposed to identify m6A sites. Methods: In order to facilitate researchers to select appropriate methods for identifying m6A sites, it is necessary to give a comprehensive review and comparison on existing methods. Results: Since researches on m6A in Saccharomyces cerevisiae are relatively clear, in this review, we summarized recent progresses on computational prediction of m6A sites in S. cerevisiae and assessed the performance of existing computational methods. Finally, future directions of computationally identifying m6A sites were presented. Conclusion: Taken together, we anticipate that this review will provide important guides for computational analysis of m 6A modifications.


Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1155
Author(s):  
Naeem Islam ◽  
Jaebyung Park

RNA modification is vital to various cellular and biological processes. Among the existing RNA modifications, N6-methyladenosine (m6A) is considered the most important modification owing to its involvement in many biological processes. The prediction of m6A sites is crucial because it can provide a better understanding of their functional mechanisms. In this regard, although experimental methods are useful, they are time consuming. Previously, researchers have attempted to predict m6A sites using computational methods to overcome the limitations of experimental methods. Some of these approaches are based on classical machine-learning techniques that rely on handcrafted features and require domain knowledge, whereas other methods are based on deep learning. However, both methods lack robustness and yield low accuracy. Hence, we develop a branch-based convolutional neural network and a novel RNA sequence representation. The proposed network automatically extracts features from each branch of the designated inputs. Subsequently, these features are concatenated in the feature space to predict the m6A sites. Finally, we conduct experiments using four different species. The proposed approach outperforms existing state-of-the-art methods, achieving accuracies of 94.91%, 94.28%, 88.46%, and 94.8% for the H. sapiens, M. musculus, S. cerevisiae, and A. thaliana datasets, respectively.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanpeng Ding ◽  
Nuomin Liu ◽  
Mengge Chen ◽  
Yulian Xu ◽  
Sha Fang ◽  
...  

Abstract Background BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined. Methods Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function. Results The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA. Conclusion Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiulin Jiang ◽  
Baiyang Liu ◽  
Zhi Nie ◽  
Lincan Duan ◽  
Qiuxia Xiong ◽  
...  

AbstractN6-methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher eukaryotic cells. m6A modification is modified by the m6A methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and, removed by the demethylases, or erasers, including FTO and ALKBH5. It is recognized by m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1, also known as “readers”. Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions, especially in the initiation and progression of different types of human cancers. In this review, we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic, central nervous and reproductive systems. We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation, its regulators and downstream target genes, during cancer progression in above systems. We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lingling Shi ◽  
Rui Huang ◽  
Yongrong Lai

Abstract Background This study aimed to determine and verify the prognostic value and potential functional mechanism of signal recognition particle 14 (SRP14) in acute myeloid leukemia (AML) using a genome-wide expression profile dataset. Methods We obtained an AML genome-wide expression profile dataset and clinical prognostic data from The Cancer Genome Atlas (TCGA) and GSE12417 databases, and explored the prognostic value and functional mechanism of SRP14 in AML using survival analysis and various online tools. Results Survival analysis showed that AML patients with high SRP14 expression had poorer overall survival than patients with low SRP14 expression. Time-dependent receiver operating characteristic curves indicated that SRP14 had good accuracy for predicting the prognosis in patients with AML. Genome-wide co-expression analysis suggested that SRP14 may play a role in AML by participating in the regulation of biological processes and signaling pathways, such as cell cycle, cell adhesion, mitogen-activated protein kinase, tumor necrosis factor, T cell receptor, DNA damage response, and nuclear factor-kappa B (NF-κB) signaling. Gene set enrichment analysis indicated that SRP14 was significantly enriched in biological processes and signaling pathways including regulation of hematopoietic progenitor cell differentiation and stem cell differentiation, intrinsic apoptotic signaling pathway by p53 class mediator, interleukin-1, T cell mediated cytotoxicity, and NF-κB-inducing kinase/NF-κB signaling. Using the TCGA AML dataset, we also identified four drugs (phenazone, benzydamine, cinnarizine, antazoline) that may serve as SRP14-targeted drugs in AML. Conclusion The current results revealed that high SRP14 expression was significantly related to a poor prognosis and may serve as a prognostic biomarker in patients with AML.


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