蛋白质组学数据揭示可变剪接蛋白质变体  

Proteomics Data Reveals Alternative Splicing Proteoforms

作　　者：吴怡颖 张炜 孔德志[1] WU Yi-Ying;ZHANG Wei;KONG De-Zhi(Institute of Integrated Traditional Chinese and Western Medicine,Hebei Medical University,Shijiazhuang 050017,China)

机构地区：[1]河北医科大学中西医结合研究所,石家庄050017

出　　处：《生物化学与生物物理进展》2024年第12期3151-3162,共12页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(82174004);河北省自然科学基金(H2022206211,H2022206387)资助项目。

摘　　要：可变剪接使同一个基因产生多种不同的转录本和蛋白质,增加蛋白质多样性和功能复杂性。转录组学和蛋白质组学是鉴定可变剪接的两种主要途径,分别通过分析RNA测序数据和蛋白质测序数据来鉴定可变剪接事件和相应蛋白质产物。尽管RNA水平的可变剪接研究已经取得了一定的进展,但是对于剪接蛋白亚型的检测和区分仍然不足。本文综述了近年来对可变剪接及其生物功能,可变剪接在不同水平检测的研究进展,详细介绍利用“自下而上”的蛋白质组学数据鉴定可变剪接蛋白质变体的两种主要方法,序列数据库构建和蛋白质鉴定算法开发。鉴定不同的可变剪接蛋白质有利于认识更全面的蛋白质功能,对发现相关生物标志物和关键药物靶点具有重要意义。Alternative splicing is an important regulatory mechanism in organisms,influencing the expression of genes involved in processes such as drug metabolism,pathway activation,and apoptosis.It refers to the process of removing introns from precursor mRNA and joining the remaining exons to produce mature mRNA.During this process,different combinations of exons can result in multiple mature mRNAs.This process is known as alternative splicing.Alternative splicing allows the same gene to produce different transcript variants and protein isoforms,increasing protein diversity and functional complexity.Transcriptomics and proteomics are two main approaches for identifying alternative splicing events.Transcriptomics identifies alternative splicing by analyzing differences between RNA sequencing data and reference sequences in databases.This method relies on the development of modern sequencing technologies.It also depends on increasingly improved splicing identification algorithms.Examples of these algorithms include alignment mapping and sequencing data quality control.The other approach is proteomic data analysis,which identifies corresponding protein products.We consider alternative splicing events more meaningful when they can be detected at the protein level.Alternative splicing proteoforms can be identified using bottom-up proteomics based on mass spectrometry.Due to the high sequence similarity between these alternative splicing proteoforms,general proteomic data analysis pipelines do not achieve good discrimination between them.To improve the identification of proteoforms and obtain differentiation information for different isoforms in proteomic data,two strategies have been developed for improving data processing:the construction of special databases and targeted identification algorithms.We believe that this potential protein isoform information may play a crucial role in life science research.In terms of databases,it is not enough to only use ordinary public databases for searching.To ensure the discovery of as ma

关 键 词：可变剪接 质谱数据分析 蛋白质鉴定算法 蛋白质序列数据库 

分 类 号：Q51[生物学—生物化学] R917[医药卫生—药物分析学]