文献类型：期刊文献

英文题名：Advances in the Structure of GGGGCC Repeat RNA Sequence and Its Interaction with Small Molecules and Protein Partners

作者：Liu, Xiaole[1];Zhao, Xinyue[1];He, Jinhan[1];Wang, Sishi[1];Shen, Xinfei[1];Liu, Qingfeng[1];Wang, Shenlin[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Peking Univ, Beijing NMR Ctr, Beijing 100087, Peoples R China

年份：2023

卷号：28

期号：15

外文期刊名：MOLECULES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001045585500001)】；

基金：The work was supported by the National Natural Science Foundation of China (22274050) and the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：amyotrophic lateral sclerosis; frontotemporal dementia; C9orf72; GGGGCC; G4

摘要：The aberrant expansion of GGGGCC hexanucleotide repeats within the first intron of the C9orf72 gene represent the predominant genetic etiology underlying amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). The transcribed r(GGGGCC)(n) RNA repeats form RNA foci, which recruit RNA binding proteins and impede their normal cellular functions, ultimately resulting in fatal neurodegenerative disorders. Furthermore, the non-canonical translation of the r(GGGGCC)(n) sequence can generate dipeptide repeats, which have been postulated as pathological causes. Comprehensive structural analyses of r(GGGGCC)(n) have unveiled its polymorphic nature, exhibiting the propensity to adopt dimeric, hairpin, or G-quadruplex conformations, all of which possess the capacity to interact with RNA binding proteins. Small molecules capable of binding to r(GGGGCC)(n) have been discovered and proposed as potential lead compounds for the treatment of ALS and FTD. Some of these molecules function in preventing RNA-protein interactions or impeding the phase transition of r(GGGGCC)(n). In this review, we present a comprehensive summary of the recent advancements in the structural characterization of r(GGGGCC)(n), its propensity to form RNA foci, and its interactions with small molecules and proteins. Specifically, we emphasize the structural diversity of r(GGGGCC)(n) and its influence on partner binding. Given the crucial role of r(GGGGCC)(n) in the pathogenesis of ALS and FTD, the primary objective of this review is to facilitate the development of therapeutic interventions targeting r(GGGGCC)(n) RNA.