scholarly journals Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Ute Scheller ◽  
Kathrin Pfisterer ◽  
Steffen Uebe ◽  
Arif B. Ekici ◽  
André Reis ◽  
...  
2020 ◽  
Vol 15 ◽  
Author(s):  
Na Wang ◽  
Yukun Li ◽  
Sijing Liu ◽  
Liu Gao ◽  
Chang Liu ◽  
...  

Background: Recent studies revealed that the hypoglycemic hormone, glucagon-like peptide-1 (GLP-1), acted as an important modulator in osteogenesis of bone marrow derived mesenchymal stem cells (BMSCs). Objectives: The aim of this study was to identify the specific microRNA (miRNA) using bioinformatics analysis and validate the presence of differentially expressed microRNAs with their target genes after GLP-1 receptor agonist (GLP-1RA) administration involved in ostogenesis of BMSCs. Methods: MiRNAs were extracted from BMSCs after 5 days’ treatment and sent for high-throughput sequencing for differentially expressed (DE) miRNAs analyses. Then the expression of the DE miRNAs verified by the real-time RT-PCR analyses. Target genes were predicted, and highly enriched GOs and KEGG pathway analysis were conducted using bioinformatics analysis. For the functional study, two of the target genes, SRY (sex determining region Y)-box 5 (SOX5) and G protein-coupled receptor 84 (GPR84), were identified. Results: A total of 5 miRNAs (miRNA-509-5p, miRNA-547-3p, miRNA-201-3p, miRNA-201-5p, and miRNA-novel-272-mature) were identified differentially expressed among groups. The expression of miRNA-novel-272-mature were decreased during the osteogenic differentiation of BMSCs, and GLP-1RA further decreased its expression. MiRNA-novel-272-mature might interact with its target mRNAs to enhance osteogenesis. The lower expression of miRNA-novel-272-mature led to an increase in SOX5 and a decrease in GPR84 mRNA expression, respectively. Conclusions: Taken together, these results provide further insights to the pharmacological properties of GLP-1RA and expand our knowledge on the role of miRNAs-mRNAs regulation network in BMSCs’ differentiation.


2021 ◽  
Vol 7 (13) ◽  
pp. eabf3072
Author(s):  
Y. Nagayoshi ◽  
T. Chujo ◽  
S. Hirata ◽  
H. Nakatsuka ◽  
C.-W. Chen ◽  
...  

FtsJ RNA 2′-O-methyltransferase 1 (FTSJ1) gene has been implicated in X-linked intellectual disability (XLID), but the molecular pathogenesis is unknown. We show that Ftsj1 is responsible for 2′-O-methylation of 11 species of cytosolic transfer RNAs (tRNAs) at the anticodon region, and these modifications are abolished in Ftsj1 knockout (KO) mice and XLID patient–derived cells. Loss of 2′-O-methylation in Ftsj1 KO mouse selectively reduced the steady-state level of tRNAPhe in the brain, resulting in a slow decoding at Phe codons. Ribosome profiling showed that translation efficiency is significantly reduced in a subset of genes that need to be efficiently translated to support synaptic organization and functions. Ftsj1 KO mice display immature synaptic morphology and aberrant synaptic plasticity, which are associated with anxiety-like and memory deficits. The data illuminate a fundamental role of tRNA modification in the brain through regulation of translation efficiency and provide mechanistic insights into FTSJ1-related XLID.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ti-Dong Shan ◽  
Han Yue ◽  
Xue-Guo Sun ◽  
Yue-Ping Jiang ◽  
Li Chen

Abstract Background The complications caused by diabetes mellitus (DM) are the focus of clinical treatment. However, little is known about diabetic enteropathy (DE) and its potential underlying mechanism. Methods Intestinal epithelial cells (IECs) and intestinal epithelial stem cells (IESCs) were harvested from BKS.Cg-Dock7m+/+Leprdb/JNju (DM) mice, and the expression of R-Spondin 3 (Rspo3) was detected by RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence. The role of Rspo3 in the abnormal differentiation of IECs during DM was confirmed by knockdown experiments. Through miRNA expression profiling, bioinformatics analysis, and RT-qPCR, we further analyzed the differentiation-related miRNAs in the IECs from mice with DM. Results Abnormal differentiation of IECs was observed in the mice with DM. The expression of Rspo3 was upregulated in the IECs from the mice with DM. This phenomenon was associated with Rspo3 overexpression. Additionally, Rspo3 is a major determinant of Lgr5+ stem cell identity in the diabetic state. Microarray analysis, bioinformatics analysis, and luciferase reporter assays revealed that microRNA (miR)-380-5p directly targeted Rspo3. Moreover, miR-380-5p upregulation was observed to attenuate the abnormal differentiation of IECs by regulating Rspo3 expression. Conclusions Together, our results provide definitive evidence of the essential role of Rspo3 in the differentiation of IECs in DM.


2017 ◽  
Vol 173 (3) ◽  
pp. 716-720 ◽  
Author(s):  
Caroline McCool ◽  
Adiaha Spinks-Franklin ◽  
Lenora M. Noroski ◽  
Lorraine Potocki

2013 ◽  
Vol 44 (05) ◽  
pp. 268-271 ◽  
Author(s):  
Moneef Shoukier ◽  
Sigrid Fuchs ◽  
Eva Schwaibold ◽  
Michael Lingen ◽  
Jutta Gärtner ◽  
...  

1995 ◽  
Vol 15 (4) ◽  
pp. 2231-2244 ◽  
Author(s):  
S Zhang ◽  
M J Ruiz-Echevarria ◽  
Y Quan ◽  
S W Peltz

In both prokaryotes and eukaryotes, nonsense mutations in a gene can enhance the decay rate or reduce the abundance of the mRNA transcribed from that gene, and we call this process nonsense-mediated mRNA decay. We have been investigating the cis-acting sequences involved in this decay pathway. Previous experiments have demonstrated that, in addition to a nonsense codon, specific sequences 3' of a nonsense mutation, which have been defined as downstream elements, are required for mRNA destabilization. The results presented here identify a sequence motif (TGYYGATGYYYYY, where Y stands for either T or C) that can predict regions in genes that, when positioned 3' of a nonsense codon, promote rapid decay of its mRNA. Sequences harboring two copies of the motif from five regions in the PGK1, ADE3, and HIS4 genes were able to function as downstream elements. In addition, four copies of this motif can function as an independent downstream element. The sequences flanking the motif played a more significant role in modulating its activity when fewer copies of the sequence motif were present. Our results indicate the sequences 5' of the motif can modulate its activity by maintaining a certain distance between the sequence motif and the termination codon. We also suggest that the sequences 3' of the motif modulate the activity of the downstream element by forming RNA secondary structures. Consistent with this view, a stem-loop structure positioned 3' of the sequence motif can enhance the activity of the downstream element. This sequence motif is one of the few elements that have been identified that can predict regions in genes that can be involved in mRNA turnover. The role of these sequences in mRNA decay is discussed.


2010 ◽  
Vol 1 (2) ◽  
pp. 230-239 ◽  
Author(s):  
Roberto Gherzi ◽  
Ching‐Yi Chen ◽  
Michele Trabucchi ◽  
Andres Ramos ◽  
Paola Briata
Keyword(s):  

2020 ◽  
Vol 8 (1) ◽  
pp. 101-111
Author(s):  
Alifah Nuke Febrianty ◽  
Alabanyo Brebahama ◽  
Melok Roro Kinanthi

Tunagrahita merupakan salah satu jenis disabilitas yang membuat penyandangnya memiliki inteligensi jauh di bawah rata-rata serta kemampuan bina bantu diri yang terbatas. Hambatan tersebut membuat anak tunagrahita menjadi kurang mandiri sehingga orang tua harus memberikan perhatian serta bantuan yang lebih besar dibandingkan dengan anak pada umumnya. Hal inilah yang dapat menjadi stressor bagi keluarga terutama ibu yang merupakan caregiver utama pada anak karena ibulah yang paling banyak meluangkan waktu untuk pengasuhan sang anak. Oleh karena itu dibutuhkan ketangguhan keluarga dalam menghadapi masalah terkait kehadiran anak tunagrahita. Resiliensi keluarga dianggap sukses bila keluarga dapat bertahan dari kesulitan dan mengambil makna dari kesulitan yang dihadapi. Salah satu cara untuk dapat resilien adalah dengan mengembangkan pandangan positif saat menghadapi masalah yang disebut juga sebagai koherensi keluarga. Penelitian ini bertujuan untuk mengetahui sejauh mana peran koherensi keluarga terhadap resiliensi keluarga yang memiliki anak tunagrahita dari perspektif ibu. Partisipan pada penelitian ini sebanyak 60 orang ibu yang memiliki anak tunagrahita, berdomisili di wilayah Jakarta, Bogor, Depok, Tangerang, dan Bekasi yang dipilih menggunakan metode  purposive sampling ­. Alat ukur yang digunakan yaitu Walsh Family Resilience Questionnaire (WFRQ) untuk mengukur resiliensi keluarga dan Family Sense of Coherence Scale (FSOCS) untuk mengukur family sense of coherence. Berdasarkan hasil uji regresi, didapatkan hasil bahwa family sense of coherence berperan secara signifikan (p 0,05) terhadap resiliensi keluarga (R-square= 0,235). Hal ini berarti koherensi keluarga berperan sebesar 23,5% terhadap resiliensi keluarga dan 76,5% lainnya dipengaruhi oleh faktor lain. Terkait dengan hal ini, upaya meningkatkan resiliensi keluarga dapat dilakukan dengan membantu keluarga mengembangkan perspektif positif dalam melihat situasi yang terjadi, menumbuhkan optimisme, dan mengedukasi keluarga untuk dapat memanfaatkan sumber daya di sekitarnya untuk membantu atasi situasi. Intellectual disability is the one of disability in which the individu has intellectual far below the average, and limitation in activity daily living. This limitation makes the children with intellectual disability have low autonomy cause parents should give care and assitaant more then usual. This condition can be the one of stressor for family, especially for the mother as caregiver who give more time to practice parenting for their children. So, family resillience is very important to face the emergence of intellectual disability children in family. In order to be resillient, a family should have positive perspective when facing the problem, called sense of coherence. The purpose of this research is finding the role of family sense of coherence towards family resillience among family who has intellectual disability children. The participant of this research is 60 mothers who have intellectual disability children and live in Jakarta, Bogor, Depok, Tangerang, and Bekasi (Jabodetabek). The participants is selected by using purposive sampling method. This research uesd Family Resilience Questionnaire (WFRQ) to measure family resillience, and Family Sense of Coherence Scale (FSOCS) to measure family sense of corerence. Based on regression test, family sense of corerence has significant role towards family resilience (R Square = 0,235, p 0,05). It meanse that family sense of coherence gives contribution about 23,5 % to family resillience, and 76,5 % influenced by another factors. As the conslusion, family can be more resillient if it develops positive perspective when facing problem, build optimism, and use every resources wisely in order to solve problem. 


2021 ◽  
Author(s):  
Sarah E. Fritz ◽  
Soumya Ranganathan ◽  
J. Robert Hogg

AbstractThe nonsense-mediated mRNA decay (NMD) pathway monitors translation termination to degrade transcripts with premature stop codons and regulate thousands of human genes. Due to the major role of NMD in RNA quality control and gene expression regulation, it is important to understand how the pathway responds to changing cellular conditions. Here we show that an alternative mammalian-specific isoform of the core NMD factor UPF1, termed UPF1LL, enables condition-dependent remodeling of NMD specificity. UPF1LL associates more stably with potential NMD target mRNAs than the major UPF1SL isoform, expanding the scope of NMD to include many transcripts normally immune to the pathway. Unexpectedly, the enhanced persistence of UPF1LL on mRNAs supports induction of NMD in response to rare translation termination events. Thus, while canonical NMD is abolished by translational repression, UPF1LL activity is enhanced, providing a mechanism to rapidly rewire NMD specificity in response to cellular stress.


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