Progress in the study of G-quadruplex interacting proteins

G-quadruplex (G4) is a noncanonical nucleic acid secondary structure formed by regular guanine repeat. G4 structure has been proven to participate in various physiological and pathological processes, such as telomere maintenance, transcription, translation, and carcinogenesis. Although Putative G-quadruplex forming sequences (PQSs) have been proven to be widely present in genome and transcriptome, the structure is highly heterogeneous among different cell types and cell cycles. G4 structures are regulated by corresponding proteins (G4-interacting proteins), for instance, nucleolin was reported to stabilize G4 structures, and DHX36 on the contrary unfolds G4s. Therefore, the study of the G4 structure and their interacting proteins will be beneficial to further reveal the regulation mechanism of biological activity and promote the development of new disease therapeutic methods. There are multiple G4 helicases in cells, in order to maintain normal physiological activity, such as the RecQ family, DEAD-box family, and DEAH-box family. The G4 structure encountered in the progression of the replication fork may prevent the passage of DNA polymerase, resulting in the arrest of the replication fork, which may result in deletion and mutation of the genome. The G quadruplex structure in the process of genome transcription has a double function. On the one hand, the G4 structure blocks the passage of RNA polymerase, resulting in the decrease of transcription level. On the other hand, studies have shown that the special structure of G4 can be used as the binding site for transcription factors to regulate transcription. Interestingly, researchers have also found some proteins that play a dual role in the folding and unfolding of G4 structures, such as topoisomerase. Human telomere DNA sequence is one of the first G4 structures to be discovered, and POT1 in the telomere protein complex is able to interact with telomere G4 and play a crucial role in maintaining chromosome stability. In addition, some G4 helicases such as CST and RPA can be bind to the G4 and open the G4 structure, helping to solve the replication pressure of the telomere. Compared with DNA, RNA is more likely to form a G4 structure under physiological conditions due to its single-stranded characteristics. High throughput sequencing and fluorescence imaging techniques have also confirmed that a large number of RNA G-quadruplex (rG4) exist in cells, and rG4 is mainly concentrated in the 5 ' and 3 ' UTR regions. Studies have shown that RNA G-quadruplex plays an important role in alternative splicing, translation regulation, and transcription termination. It is reported that G4 interacting proteins play an important role in the regulation of nucleic acids epigenetic modification, such as DNA methyltransferase DNMTs and RNA methyltransferase METTL14, which have been shown to bind specifically to G4 and regulate the nucleic acid methylation process. Moreover, G4 interacting proteins play important roles in histone methylation and chromatin remodeling. Therefore, the identification and in-depth study of G4-interacting proteins will help to reveal the mechanism of G4-protein interaction and its biological role in vivo. In recent years, benefiting from the progress in the study of nucleic acid-protein interaction and the development of new technology for the study of G-quadruplex interacting proteins, scientists have discovered a variety of G-quadruplex interacting proteins involved in a variety of biological processes. In this paper, we introduced the types and functions of known G4 interacting proteins, reviewed the recent development of research methods of G-quadruplex interacting proteins, and blueprint the forward development.