| 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) |