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Sequential Polyadenylation to Enable Alternative mRNA 3’ End Formation
Xiang-Dong Fu,Yajing Hao,Ting Cai,Chang Liu,Xuan Zhang 한국분자세포생물학회 2023 Molecules and cells Vol.46 No.1
In eukaryotic cells, a key RNA processing step to generate mature mRNA is the coupled reaction for cleavage and polyadenylation (CPA) at the 3′ end of individual transcripts. Many transcripts are alternatively polyadenylated (APA) to produce mRNAs with different 3′ ends that may either alter protein coding sequence (CDS-APA) or create different lengths of 3′UTR (tandem-APA). As the CPA reaction is intimately associated with transcriptional termination, it has been widely assumed that APA is regulated cotranscriptionally. Isoforms terminated at different regions may have distinct RNA stability under different conditions, thus altering the ratio of APA isoforms. Such differential impacts on different isoforms have been considered as post-transcriptional APA, but strictly speaking, this can only be considered “apparent” APA, as the choice is not made during the CPA reaction. Interestingly, a recent study reveals sequential APA as a new mechanism for post-transcriptional APA. This minireview will focus on this new mechanism to provide insights into various documented regulatory paradigms.
Mechanical evaluation of polymer microneedles for transdermal drug delivery: In vitro and in vivo
Rui Xuan Liu,Yu Ting He,Ling Liang,Liu Fu Hu,Yue Liu,Rui-xing Yu,Bo Zhi Chen,Yong Cui,Xin Dong Guo 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.114 No.-
In this study, we reported two types of PMNs based on polylactic acid (PLA) and polyvinyl alcohol (PVA),respectively. Parafilm M film, porcine skin, and rats’ models were operated to evaluate the mechanicalproperties in vitro and in vivo to find optimal parameters for efficient insertion. Insertion depth was measuredusing Digital Force Gauge by changing insertion force and speed, respectively. Results showed thatincreasing the insertion force and speed used for PMNs application led to a significant increase in thedepth of insertion. A force of 18 N under a speed of 330 mm/min was the optimal condition for insertingPMNs array into ParafilmM film and porcine skin. In addition, PLA-MNs exhibited higher robustness andenhanced homogeneity in insertion depth compared with PVA-MNs, but PVA-MNs were able to reachmuch deeper insertion depth. Moreover, Sprague Dawley (SD) rat experiments confirmed the effectivenessof optimal insertion parameters for transdermal drug delivery. This study illustrated not only thedevelopment of novel PMNs but also the mechanical evaluation for the design of PMNs.
Jian-Wei Lv,Wei Wen,Chen Jiang,Qi-Bo Fu,Yin-Jun Gu,Ting-Ting Lv,Zhen-Dong Li,Wei Xue 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-
Our study aims to investigate the roles that microRNA-214 (miR-214) plays in the epithelial mesenchymal transition (EMT) process and the development of interstitial cystitis (IC) in postmenopausal women by targeting Mitofusin 2 (Mfn2). IC bladder tissues and adjacent normal bladder tissues were collected from postmenopausal women. Immunohistochemistry (IHC) staining was conducted. The target relationship between miR-214 and Mfn2 was determined by a dual luciferase reporter gene assay. Adipose-derived mesenchymal stem cells (ADMSCs) were extracted from postmenopausal rats and assigned to the blank, mimics, miR-214 inhibitors, mimics negative control (NC), inhibitors NC, Mfn2 siRNA, miR-214 inhibitors and Mfn2 siRNA groups. Exosomes secreted by transfected ADMSCs were instilled into the bladders of postmenopausal rats. The expression of miR-214 and Mfn2 mRNA and EMT markers was assessed by qRT-PCR and western blotting. It was confirmed that Mfn2 was the target gene of miR-214 in IC. Compared with the normal bladder tissues, miR-214 decreased, but Mfn2 increased in IC bladder tissues. Compared with the blank group, the expression of miR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein increased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein decreased in the miR-214 mimics and Mfn2 groups. The expression of MiR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein decreased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein increased in the miR-214 inhibitors group. Our findings indicate that the inhibition of miR-214 promotes the EMT process and contributes to bladder wall fibrosis by up-regulating Mfn2, thus leading to the occurrence of IC in postmenopausal women.
Pan Ying-Hua,Nong Bao-Xuan,Chen Lei,Yang Xing-Hai,Xia Xiu-Zhong,Zhang Zong-Qiong,Qing Dong-Jin,Gao Ju,Huang Cheng-Cui,Li Dan-Ting,Deng Guo-Fu 한국유전학회 2023 Genes & Genomics Vol.45 No.7
Background Cold damage stress significantly affects rice growth (germination and seedling) and causes serious losses in yield in temperate and high-altitude areas around the globe. Objective This study aimed to explore the cold tolerance (CT) locus of rice and create new cold-tolerant germplasm. We constructed a chromosome segment substitution line (CSSL) with strong CT and fine mapped quantitative trait loci (QTLs) associated with CT by performing the whole-genome resequencing of CSSL with phenotypes under cold treatment. Methods A chromosome CSSL, including 271 lines from a cross between the cold-tolerant wild rice Y11 (Oryza rufipogon Griff.) and the cold-sensitive rice variety GH998, was developed to map QTLs conferring CT at the germination stage. The whole-genome resequencing was performed on CSSL for mapping QTLs of associated with CT at the germination stage. Results A high-density linkage map of the CSSLs was developed using the whole-genome resequencing of 1484 bins. The QTL analysis using 615,466 single-nucleotide polymorphisms (SNPs) led to the identification of 2 QTLs related to germination rate at low-temperature on chromosome 8 (qCTG-8) and chromosome 11 (qCTG-11). The qCTG-8 and qCTG-11 explained 14.55% and 14.31% of the total phenotypic variation, respectively. We narrowed down qCTG-8 and qCTG-11 to 195.5 and 78.83-kb regions, respectively. The expression patterns of important candidate genes in different tissues, and of RNA-sequencing (RNA-seq) in CSSLs, were identified based on gene sequences in qCTG-8 and qCTG-11 cold-induced expression analysis. LOC_Os08g01120 and LOC_Os08g01390 were identified as candidate genes in qCTG-8, and LOC_Os11g32880 was identified as a candidate gene in qCTG-11. Conclusions This study demonstrated a general method that could be used to identify useful loci and genes in wild rice and aid in the future cloning of candidate genes of qCTG-8 and qCTG-11. The CSSLs with strong CT were supported for breeding cold-tolerant rice varieties.