Role of an intranuclear network organized by SAF-A/RNA supramolecular structure in chromatin dynamics and transcription

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03190
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: NOZAWA Ryusuke 公益財団法人がん研究会, がん研究所 実験病理部, 研究員 (70868710)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: クロマチン / 超解像顕微鏡 / RNA / 転写 / SAF-A

Outline of Final Research Achievements

Cells create diverse microenvironments within the nucleus by concentrating molecules, thereby regulating fundamental cellular functions such as transcription. However, due to limited understanding of the spatial control of related molecules and the dynamics of chromatin polymer, it remains enigmatic how these biochemical reactions proceed appropriately and efficiently. To address this question, we have investigated the morphology and structural properties of the dynamic mesh formed by nuclear RNA and SAF-A (scaffold attachment factor A, or hnRNP U), as well as its mechanistic role in modulating chromatin decompaction. We reveal a novel mechanism whereby newly synthesized RNA interacts with SAF-A, forming an interconnected supramolecular network degraded by the exonuclease XRN2, leading to dynamic cycles of gelation and fluidization. This network decreases protein mobility and regulates chromatin compaction by modulating local viscosity, thereby opening transcriptionally active regions.

Free Research Field

クロマチン構造

Academic Significance and Societal Importance of the Research Achievements

本研究から、転写が誘導するSAF-A/RNAの構造体の形成によって、その局所に粘性がもたらされ、また一方でXRN2が備えるRNAの分解活性により、SAF-A/RNA構造体が破壊される、というダイナミックなサイクルの存在が明らかとなった。本研究成果は、細胞核内の分子の流動性を制御する分子メカニズムの一端を示すともに、SAF-Aの遺伝子変異が同定されている神経変性疾患の細胞病態を理解する新たな視点を提供することが期待される。