Hypoxia‐dependent mRNA expression pattern of splicing factor YT521 and its impact on oncological important target gene expression

生物 基因表达 基因 缺氧(环境) 信使核糖核酸 RNA剪接 选择性拼接 遗传学 表达式(计算机科学) 细胞生物学 计算生物学 核糖核酸 氧气 程序设计语言 化学 有机化学 计算机科学
作者
Marc Hirschfeld,Bo Zhang,Markus Jaeger,Stefan Stamm,Thalia Erbes,Sebastian Mayer,Xiaowen Tong,Elmar Stickeler
出处
期刊:Molecular Carcinogenesis [Wiley]
卷期号:53 (11): 883-892 被引量:30
标识
DOI:10.1002/mc.22045
摘要

Abstract The ubiquitously expressed splicing factor YT521 (YTHDC1) is characterized by alternatively spliced isoforms with regulatory impact on cancer‐associated gene expression. Our recent findings account for the prognostic significance of YT521 in endometrial cancer. In this study, we investigated the hypoxia‐dependency of YT521 expression as well as its differential isoform activities on oncological important target genes. YT521's potential regulatory influence on splicing was investigated by a minigene assay for the specific target gene CD44. Functional splicing analysis was performed by YT521 knock‐down or overexpression, respectively. In addition, YT521 expression was determined under hypoxia. The two protein‐generating YT521 mRNA isoforms 1 and 2 caused a comparable, specific induction of CD44v alternative splicing ( P < 0.01). In a number of oncological target genes, YT521 upregulation significantly altered BRCA2 expression pattern, while YT521 knock‐down created a significant regulatory impact on PGR expression, respectively. Hypoxia induced a specific switch towards the processing of two non‐protein‐coding mRNA variants, of which one is described for the first time in this study. The presented study underlines the comparable regulatory potential of both YT521 isoforms 1 and 2, on the investigated target genes in vivo and in vitro. Hypoxia induces a specific switch in YT521 expression pattern towards the two non‐protein coding mRNA variants, the already characterized isoform 3 and the newly discovered exon 8‐skipping isoform. The altered YT521 alternative splicing is functionally coupled with nonsense‐mediated decay and can be interpreted as regulated unproductive splicing and transcription with consecutive impact on the processing of specific cancer‐associated genes, such as BRCA2 and PGR. © 2013 Wiley Periodicals, Inc.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
复方蛋酥卷完成签到,获得积分10
1秒前
1秒前
哈哈哈哈完成签到,获得积分20
1秒前
打打应助杨昊采纳,获得10
2秒前
科研通AI2S应助太阳采纳,获得10
3秒前
wangkeke完成签到,获得积分10
3秒前
维尼发布了新的文献求助10
5秒前
科研通AI2S应助湖里采纳,获得10
5秒前
丘比特应助zzzyq0063采纳,获得10
6秒前
情怀应助王木木采纳,获得20
6秒前
中中中发布了新的文献求助10
6秒前
哭泣初夏完成签到 ,获得积分10
6秒前
11秒前
Tu完成签到,获得积分10
11秒前
久晴完成签到,获得积分10
12秒前
伶俐绿海完成签到 ,获得积分10
12秒前
冷艳的小懒虫完成签到 ,获得积分10
13秒前
善学以致用应助Tu采纳,获得10
13秒前
13秒前
15秒前
Jasper应助湖里采纳,获得10
15秒前
16秒前
科研通AI2S应助未明的感觉采纳,获得10
19秒前
曦子曦子应助搞怪的雨南采纳,获得10
19秒前
橘子海冒险完成签到,获得积分10
20秒前
我是老大应助开心元霜采纳,获得10
21秒前
科研通AI2S应助beibei采纳,获得10
22秒前
22秒前
现代乌龟完成签到,获得积分10
23秒前
认真雅阳发布了新的文献求助10
23秒前
23秒前
王木木发布了新的文献求助20
24秒前
聪慧的诗兰完成签到,获得积分10
24秒前
吉祥应助湖里采纳,获得10
25秒前
25秒前
25秒前
Robin发布了新的文献求助10
27秒前
27秒前
27秒前
意安发布了新的文献求助10
28秒前
高分求助中
Sustainability in Tides Chemistry 1500
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Threaded Harmony: A Sustainable Approach to Fashion 799
Livre et militantisme : La Cité éditeur 1958-1967 500
Retention of title in secured transactions law from a creditor's perspective: A comparative analysis of selected (non-)functional approaches 500
"Sixth plenary session of the Eighth Central Committee of the Communist Party of China" 400
New China Forges Ahead: Important Documents of the Third Session of the First National Committee of the Chinese People's Political Consultative Conference 400
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3056002
求助须知:如何正确求助?哪些是违规求助? 2712582
关于积分的说明 7432387
捐赠科研通 2357594
什么是DOI,文献DOI怎么找? 1248929
科研通“疑难数据库(出版商)”最低求助积分说明 606823
版权声明 596195