Bioinformatic Analysis Reveals the Distinct Role of 5’UTR-specific m6A RNA Modification in Mice Developing Cerebral Cortices

2021 ◽  
Author(s):  
Long-Bin Zhang ◽  
Ting-Ting Qiu ◽  
Wu-Wei-Jie Yang

N6-methyladenosine (m6A) abundantly exists in the cerebral cortex, and is emerging as an essential factor in cortical development and function. As the m6A binding site appears to be dynamically methylated in different RNA regions at the temporal-specific developing stage, it is of value to distinguish the unique character of region- and temporal-specific m6A. Herein, we analyzed the status of temporal-specific m6A within RNA 5’ untranslated region (5’UTR) using m6A-methylated sequencing data and transcriptomic sequencing data from 12.5-13-day embryonic cerebral cortices and 14-day postnatal ones. We identified sorts of RNAs that are uniquely m6A-methylated in the 5’UTR region and sorted them into specific neurological processes. Compared with 3’UTR-m6A-methylated RNAs, 5’UTR-m6A-methylated RNAs showed unique functions and mechanisms in regulating cortical development, especially through the pathway of mRNA transport and surveillance. Moreover, the 5’UTR-specific m6A was associated with neurological disorders as well. The FoxO signaling pathway was then focused by these pathogenic 5’UTR-m6A-methylated RNAs, and explored to be involved in the determination of neurological disorders. Additionally, the 5’UTR-m6A-modification patterns and transcriptional patterns play independent but cohesive roles in the developing cortices. Our study emphasizes the importance of 5’UTR-specific m6A in the developing cortex and provides an informative reference for future studies of 5’UTR-specific m6A in normal cortical development and neurological disorders.

2019 ◽  
Author(s):  
Xinxin Zhang ◽  
Yilong Yao ◽  
Jinghua Han ◽  
Yalan Yang ◽  
Yun Chen ◽  
...  

AbstractBackgroundN6-methyladenosine (m6A) is the most abundant RNA modification and essentially participates in the regulation of skeletal muscle development. However, the status and function of m6A methylation in prenatal myogenesis remains unclear now.ResultsIn our present study, we first demonstrate that chemical suppression of m6A and knockdown METTL14 significantly inhibit the differentiation and promote the proliferation of C2C12 myoblast cells. The mRNA expression of m6A reader protein IGF2BP1, which functions to promote the stability of target mRNA, continually decreases during the prenatal skeletal muscle development. Thereafter, profiling transcriptome-wide m6A for six developmental stage of prenatal skeletal muscle, which spanning two important waves of pig myogenesis, were performed using a refined MeRIP sequencing technology that is optimal for small-amount of RNA samples. Highly dynamic m6A methylomes across different development stages were then revealed, with majority of the affected genes enriched in pathways of skeletal muscle development. In association with the transcriptome-wide alterations, transcriptional regulatory factors (MyoD) and differentiated markers (MyHC, MYH1) of muscle development are simultaneously regulated with m6A and IGF2BP1. Knockdown of IGF2BP1 also suppresses myotube formation and promotes cell proliferation.ConclusionsThe present study clarifies the dynamics of RNA m6A methylation in the regulation of prenatal skeletal muscle development, providing a data baseline for future developmental as well as biomedical studies of m6A functions in muscle development and disease.


2021 ◽  
Vol 22 (5) ◽  
pp. 2647
Author(s):  
M. Quadir Siddiqui ◽  
Maulik D. Badmalia ◽  
Trushar R. Patel

Members of the human Zyxin family are LIM domain-containing proteins that perform critical cellular functions and are indispensable for cellular integrity. Despite their importance, not much is known about their structure, functions, interactions and dynamics. To provide insights into these, we used a set of in-silico tools and databases and analyzed their amino acid sequence, phylogeny, post-translational modifications, structure-dynamics, molecular interactions, and functions. Our analysis revealed that zyxin members are ohnologs. Presence of a conserved nuclear export signal composed of LxxLxL/LxxxLxL consensus sequence, as well as a possible nuclear localization signal, suggesting that Zyxin family members may have nuclear and cytoplasmic roles. The molecular modeling and structural analysis indicated that Zyxin family LIM domains share similarities with transcriptional regulators and have positively charged electrostatic patches, which may indicate that they have previously unanticipated nucleic acid binding properties. Intrinsic dynamics analysis of Lim domains suggest that only Lim1 has similar internal dynamics properties, unlike Lim2/3. Furthermore, we analyzed protein expression and mutational frequency in various malignancies, as well as mapped protein-protein interaction networks they are involved in. Overall, our comprehensive bioinformatic analysis suggests that these proteins may play important roles in mediating protein-protein and protein-nucleic acid interactions.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Anastasiya Börsch ◽  
Daniel J. Ham ◽  
Nitish Mittal ◽  
Lionel A. Tintignac ◽  
Eugenia Migliavacca ◽  
...  

AbstractSarcopenia, the age-related loss of skeletal muscle mass and function, affects 5–13% of individuals aged over 60 years. While rodents are widely-used model organisms, which aspects of sarcopenia are recapitulated in different animal models is unknown. Here we generated a time series of phenotypic measurements and RNA sequencing data in mouse gastrocnemius muscle and analyzed them alongside analogous data from rats and humans. We found that rodents recapitulate mitochondrial changes observed in human sarcopenia, while inflammatory responses are conserved at pathway but not gene level. Perturbations in the extracellular matrix are shared by rats, while mice recapitulate changes in RNA processing and autophagy. We inferred transcription regulators of early and late transcriptome changes, which could be targeted therapeutically. Our study demonstrates that phenotypic measurements, such as muscle mass, are better indicators of muscle health than chronological age and should be considered when analyzing aging-related molecular data.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chong Chu ◽  
Rebeca Borges-Monroy ◽  
Vinayak V. Viswanadham ◽  
Soohyun Lee ◽  
Heng Li ◽  
...  

AbstractTransposable elements (TEs) help shape the structure and function of the human genome. When inserted into some locations, TEs may disrupt gene regulation and cause diseases. Here, we present xTea (x-Transposable element analyzer), a tool for identifying TE insertions in whole-genome sequencing data. Whereas existing methods are mostly designed for short-read data, xTea can be applied to both short-read and long-read data. Our analysis shows that xTea outperforms other short read-based methods for both germline and somatic TE insertion discovery. With long-read data, we created a catalogue of polymorphic insertions with full assembly and annotation of insertional sequences for various types of retroelements, including pseudogenes and endogenous retroviruses. Notably, we find that individual genomes have an average of nine groups of full-length L1s in centromeres, suggesting that centromeres and other highly repetitive regions such as telomeres are a significant yet unexplored source of active L1s. xTea is available at https://github.com/parklab/xTea.


Author(s):  
Shunjiang Ma ◽  
Gaicheng Liu ◽  
Zhiwu Huang

With the development of sports in colleges and universities, the research on innovation reform of sports industry has been deepened. Therefore, based on the above situation, a study of the status quo and development direction of sports industry in colleges and universities based on the Euclid algorithm is proposed. In the research here, according to the traditional sports industry concept to sum up, and then according to the advantages of computer technology to deal with the relevant data. In order to realize good overlap between data, an application of Euclidean algorithm is proposed. In the test of Euclidean algorithm, the efficiency and function of the algorithm are tested comprehensively, and the test results show that the research is feasible.


1958 ◽  
Vol 52 (2) ◽  
pp. 260-279 ◽  
Author(s):  
Kenneth S. Carlston

It is the purpose of this article to investigate the status of concession agreements in the light of the rules of international law bearing on the power of a state to nationalize property. It is a continuation of an earlier article which explored the nature and function of the concession agreement in the national and international economies. The first article rested on the assumption that legal rules could not be fully understood or evaluated without a fairly clear understanding of the social facts which they were designed to regulate.


2021 ◽  
Vol 134 (16) ◽  

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Fanny Jaudon and Martina Albini are co-first authors on ‘ A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor’, published in JCS. Fanny is a postdoc at the University of Trieste in the lab of Lorenzo A. Cingolani at Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Genova, Italy, investigating the molecular mechanisms controlling development and function of neuronal circuits and implementing genome-editing approaches for the treatment of neurological disorders. Martina is a PhD student at the Istituto Italiano di Tecnologia in the lab of Fabio Benfenati and Fabrizia Cesca investigating neurotrophin biology and its involvement in neurological diseases.


2015 ◽  
Vol 77 (22) ◽  
Author(s):  
Candra Dewi ◽  
Ratna Putri P.S ◽  
Indriati Indriati

Information about the status of disease (prognosis) for patients with hepatitis is important to determine the type of action to stabilize and cure this disease. Among some system, fuzzy system is one of the methods that can be used to obtain this prognosis. In the fuzzification process, the determination of the exact range of membership function will influence the calculation of membership degree and of course will affect the final value of fuzzy system. This range and function can usually be formed using intuition or by using an algorithm. In this paper, Particle Swarm Optimization (PSO) algorithm is implemented to form the triangular membership functions in the case of patients with hepatitis. For testing process, this paper conducts four scenarios to find the best combination of PSO parameter values . Based on the testing it was found that the best parameters to form a membership function range for the hepatitis data is about 0.9, 0.1, 2, 2, 100, 500 for inertia max, inertia min, local ballast constant, global weight constant, the number of particles, and maximum iterations respectively.  


2018 ◽  
Vol 28 (2) ◽  
pp. 120-123
Author(s):  
Dugald Gardner

William Rutherford Sanders spent a childhood and early student days divided between Edinburgh and Montpelier, France before graduating in Medicine in Edinburgh. An early interest in the spleen was encouraged by a two-year period in Europe where he became familiar with the work of Helmholtz, Bernard and Henle. Returning to Edinburgh, his growing experience led to the position of assistant in the Infirmary pathology department. He conducted classes in the University of Edinburgh and on behalf of the Royal Colleges became familiar with the museum of the Royal College of Surgeons where he was chosen as Conservator in 1853. Criticised by 20th century historians for concentrating on verbal teaching rather than on the conservation of the museum, Sanders became a consultant physician to the Royal Infirmary in 1861 and in 1869 Professor of General Pathology. Throughout these years, Sanders gave as much time as possible to the study of the structure and function of the spleen and to neurological disorders such as hemiplegia. His later life was interrupted by a series of illnesses commencing with an abdominal abscess. A prolonged convalescence allowed the resumption of work but deranged vision and hemiplegia preceded his death on 18 February 1881.


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