RRC ID 85888
著者 Sahoo BR, Kocman V, Clark N, Myers N, Deng X, Wong EL, Yang HJ, Kotar A, Guzman BB, Dominguez D, Plavec J, Bardwell JCA.
タイトル Protein G-quadruplex interactions and their effects on phase transitions and protein aggregation.
ジャーナル Nucleic Acids Res
Abstract The SERF family of proteins were originally discovered for their ability to accelerate amyloid formation. Znf706 is an uncharacterized protein whose N-terminus is homologous to SERF proteins. We show here that human Znf706 can promote protein aggregation and amyloid formation. Unexpectedly, Znf706 specifically interacts with stable, non-canonical nucleic acid structures known as G-quadruplexes. G-quadruplexes can affect gene regulation and suppress protein aggregation; however, it is unknown if and how these two activities are linked. We find Znf706 binds preferentially to parallel G-quadruplexes with low micromolar affinity, primarily using its N-terminus, and upon interaction, its dynamics are constrained. G-quadruplex binding suppresses Znf706's ability to promote protein aggregation. Znf706 in conjunction with G-quadruplexes therefore may play a role in regulating protein folding. RNAseq analysis shows that Znf706 depletion specifically impacts the mRNA abundance of genes that are predicted to contain high G-quadruplex density. Our studies give insight into how proteins and G-quadruplexes interact, and how these interactions affect both partners and lead to the modulation of protein aggregation and cellular mRNA levels. These observations suggest that the SERF family of proteins, in conjunction with G-quadruplexes, may have a broader role in regulating protein folding and gene expression than previously appreciated.
巻・号 52(8)
ページ 4702-4722
公開日 2024-5-8
DOI 10.1093/nar/gkae229
PII 7640530
PMID 38572746
PMC PMC11077067
MeSH Amyloid / chemistry Amyloid / genetics Amyloid / metabolism DNA-Binding Proteins* / chemistry DNA-Binding Proteins* / metabolism G-Quadruplexes* Humans Phase Transition Protein Aggregates* Protein Binding RNA, Messenger / chemistry RNA, Messenger / genetics RNA, Messenger / metabolism
IF 11.502
リソース情報
遺伝子材料 pET-HisSumo-hZnf706 (RDB20982)