Cancer-associated dynamics and potential regulators of intronic polyadenylation revealed by IPAFinder using standard RNA-seq data.

Cancer-associated dynamics and potential regulators of intronic polyadenylation revealed by IPAFinder using standard RNA-seq data.
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IPAFinder 使用标准 RNA-seq 数据揭示了癌症相关动力学和内含子多聚腺苷酸化的潜在调节因子

DOI:
10.1101/gr.271627.120
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发表时间:
2021-11
期刊:
影响因子:
7
通讯作者:
Ni T
Ni T
中科院分区:
生物学1区
文献类型:
--
作者:
Zhao Z;Xu Q;Wei R;Wang W;Ding D;Yang Y;Yao J;Zhang L;Hu YQ;Wei G;Ni T

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内含子多聚腺苷酸化(IPA)通常导致mRNA编码区的改变,它在疾病中的意义已经被认识到,尽管它的状态很开始。方便、准确地鉴定IPA对于进一步评价其生物学意义具有重要意义。在这里,我们开发了IPAFinder,一种生物信息学方法,用于从标准RNA-seq数据中从头识别内含子PolyA位点及其动态变化。将IPAFinder应用于六种肿瘤类型的256对泛癌肿瘤/正常对照,我们发现了490个反复发生的动态变化的IPA事件,其中一些是新的,来自TSC1、SPERD2和CCND2等癌症相关基因。此外,IPAFinder发现,IPA可以受到剪接和M6A修饰相关因素的调控。总之,IPAFinder能够利用标准的RNA-SEQ数据在全球范围内发现和表征受生物调控的IPA,并应揭示IPA在各种过程中的生物学意义。
Intronic polyadenylation (IpA) usually leads to changes in the coding region of an mRNA, and its implication in diseases has been recognized, although at its very beginning status. Conveniently and accurately identifying IpA is of great importance for further evaluating its biological significance. Here, we developed IPAFinder, a bioinformatic method for the de novo identification of intronic poly(A) sites and their dynamic changes from standard RNA-seq data. Applying IPAFinder to 256 pan-cancer tumor/normal pairs across six tumor types, we discovered 490 recurrent dynamically changed IpA events, some of which are novel and derived from cancer-associated genes such as TSC1, SPERD2, and CCND2. Furthermore, IPAFinder revealed that IpA could be regulated by factors related to splicing and m6A modification. In summary, IPAFinder enables the global discovery and characterization of biologically regulated IpA with standard RNA-seq data and should reveal the biological significance of IpA in various processes.
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