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在胰腺炎症肌纤维细胞瘤中,一种替代的拼接UPF2转录

Hui Jiang¹, Yunshuo Zhang¹, Jiayang Hu²

¹Department of Pathology, First Affiliated Hospital, Changhai Hospital, Naval Medical University, 168 Changhai Road, Shanghai, 200433, China.

Biochemical and biophysical research communications

|December 6, 2023

概括

无意中介衰变 (NMD) 途径的破坏,特别是UPF2mRNA的替代拼接,通过促进免疫细胞透和潜在的肌纤维细胞增殖,有助于炎症性肌纤维细胞瘤 (IMTs).

科学领域:

在瘤学瘤学.
分子生物学分子生物学
免疫学免疫学免疫学

背景情况:

炎症性肌纤维细胞瘤 (IMTs) 表现出肌纤维细胞的增殖和炎症细胞的透.
以前的研究将NMD通路的破坏与IMT中的免疫细胞透联系起来.
在IMT中驱动肌纤维细胞分化和扩散的机制仍然不清楚.

研究的目的:

调查NMD途径在IMT发展背后的分子变化中的作用.
为了确定与肌纤维细胞增殖和IMT的分化相关的特定分子变化.

主要方法:

反转录-聚合酶链反应 (RT-PCR) 和定量PCR (RT-qPCR).
DNA 测序和西方斑点分析.
5'cDNA末端的快速放大 (5'RACE) 和特定位点的突变发生.

主要成果:

在胰腺IMT中发现了缺少第2和第3个外因子的替代拼接UPF2mRNA,导致截断的UPF2蛋白质.
在UPF2mRNA的5'未翻译区域 (5'UTR) 的上游开放读取框架 (uORF) 中介于翻译抑制,替代拼接UPF2更容易被翻译.
在IMT样本中观察到包括CDKN1A和p21在内的NMD目标的升级,这表明NMD途径受到干扰,并可能对IMT病变产生贡献.

结论:

对UPFs/NMD路径的破坏与驱动IMTs分化和扩散的分子变化有关.
这些发现表明,一种新的机制涉及IMT发展中的NMD途径功能障碍.

关键词:

没有意义的RNA衰变 (NMD)胰腺炎症肌纤维细胞瘤 (IMTs)上方框架转移2 (UPF2) 的情况.p21 (waf1/cip1) 的意思是说

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RNA Splicing

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...

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Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...