分子チャペロンであるTRAP1はLuc7l3 mRNAの翻訳を促進し,卵巣がん細胞の増殖を促進する

Sabrina De Lella¹, Lorenza Pedalino², Mehad Almagboul Abdalla Abaker¹

¹Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, 80131, Italy.

RNA (New York, N.Y.)

|September 2, 2025

まとめ

熱ショックタンパク質TRAP1はRNAを結合し,スプライシング因子LUC7L3を調節する. このRNA結合は卵巣がん細胞の増殖を促進し,新しい治療標的を明らかにします.

科学分野:

分子生物学
癌研究
RNA 生物学

背景:

熱ショックタンパク質 (HSP) は RNA インタラクトームでますます多く見られ,新しい機能を示唆しています.
がんに関連するチャペロンTRAP1は,細胞呼吸とタンパク質合成を調節することが知られているが,そのRNA結合の役割は未知のものである.

研究の目的:

TRAP1をRNA結合タンパク質 (RBP) として特徴づける.
TRAP1のRNA標的と卵巣がんの増殖におけるその役割を特定する.

主な方法:

タンパク質とRNAを中心とした方法を使用して,TRAP1 RNA結合が vivoで確認された.
卵巣がん細胞における強化されたクロスリンクと免疫プレシピテーション (eCLIP) を利用した.
RIP-qPCRを行い,mRNA翻訳と細胞増殖を評価した.

主要な成果:

TRAP1は複数の領域を通じてRNAを結合し,主に細胞タンパク質をコードする遺伝子,特にスプライシング因子を標的にします.
TRAP1は,U1のsnRNP成分であるLUC7L3を有意に結合する.
TRAP1は,LUC7L3 mRNAの翻訳を促進し,卵巣がん細胞の増殖を促進する.

結論:

TRAP1は初めてRBPとして包括的に特徴付けられています.
TRAP1媒介によるLUC7L3の転移調節は卵巣がん細胞増殖の重要な要因である.
TRAP1は卵巣がんにおける潜在的な治療標的である.

キーワード:

高度卵巣がんルック7L3 RNA結合タンパク質トラップ1 mRNA翻訳

さらに関連する動画

08:00

Defining the Program of Maternal mRNA Translation during In vitro Maturation using a Single Oocyte Reporter Assay

Published on: June 16, 2021

4.5K

08:58

In Vitro Transcribed RNA-based Luciferase Reporter Assay to Study Translation Regulation in Poxvirus-infected Cells

Published on: May 1, 2019

15.1K

関連する概念動画

02:33

Initiation of Translation

34.5K

Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...

34.5K

02:28

Leaky Scanning

5.2K

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...

5.2K

02:24

Regulation of Expression Occurs at Multiple Steps

23.2K

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...

23.2K

01:26

Bacterial Protein Maturation

Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...

02:55

The Nucleolus

9.1K

The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...

9.1K

01:22

MicroRNAs

3.1K

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...