8X0N

The molecular mechanism of hnRNPA1 recognize TERRA RNA.

8X0N の概要

• エントリーDOI: 10.2210/pdb8x0n/pdb
• 分子名称: Heterogeneous nuclear ribonucleoprotein A1, RNA (5'-R(*UP*UP*AP*GP*GP*GP*UP*UP*AP*GP*GP*G)-3') (2 entities in total)
• 機能のキーワード: hnrnpa1, up1, terra, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27041.32

構造登録者

Xu, Z.Y.,Liu, Y.,Li, F. (登録日: 2023-11-05, 公開日: 2024-11-06, 最終更新日: 2025-05-07)

主引用文献

Xu, Z.,Liu, Y.,Li, F.,Yang, Y.,Zhang, H.,Meng, F.,Liu, X.,Xie, X.,Chen, X.,Shi, Y.,Zhang, L.
Phase separation of hnRNPA1 and TERRA regulates telomeric stability.
J Mol Cell Biol, 16:-, 2025

PubMed Abstract: Telomeres are the complexes composed of repetitive DNA sequences and associated proteins located at the end of chromatin. As a result of the DNA replication ending issue, telomeric DNA shortens during each cell cycle. The shelterin protein complex caps telomeric ends and forms a high-order protein-DNA structure to protect telomeric DNA. The stability of telomeres is critical for cellular function and related to the progression of many human diseases. Telomeric repeat-containing RNA (TERRA) is a noncoding RNA transcribed from telomeric DNA regions. TERRA plays an essential role in regulating and maintaining the stability of telomeres. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins associated with complex and diverse biological processes. hnRNPA1 can recognize both TERRA and telomeric DNA. Previous research reported that hnRNPA1, TERRA, and POT1, a component of the shelterin complex, work coordinately and displace replication protein A from telomeric single-stranded DNA after DNA replication, promoting telomere capping to preserve genomic integrity. However, the detailed molecular mechanism has remained unclear for >20 years. Here, our study revealed the molecular structure through which the hnRNPA1 UP1 domain interacts with TERRA and identified critical residues on the interacting surface between UP1 and TERRA. Furthermore, we proved that nucleic acids significantly increase the phase-separating ability of hnRNPA1, while disrupting the UP1-TERRA interaction extraordinarily affects hnRNPA1 droplet formation both in vitro and in vivo. Taken together, these data reveal the molecular mechanism of the phase separation of hnRNPA1 and TERRA and the potential contribution of the droplets to maintaining genomic stability.

PubMed: 39313323
DOI: 10.1093/jmcb/mjae037

実験手法

X-RAY DIFFRACTION (2.8 Å)