RNA結合タンパク質LIN28aは,ロングノンコーディングRNA-H19を介して心臓における新しい筋細胞の形成を調節する
Vagner Oliveira Carvalho Rigaud1, Robert C Hoy1, Justin Kurian1
1Center for Metabolic Disease Research (V.0.C.R., R.C.H., J.K., C.Z., M.B., I.B., J.P., T.P., M.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Circulation
|October 31, 2022
まとめ
RNA結合タンパク質LIN28aは,単核二倍体心筋細胞の代謝を再プログラムし,その持続性を促進し,損傷後の心臓の修復を促進します. この発見は,心筋細胞の代謝とプロイドの調節と心臓の再生を関連付けています.
科学分野:
- 心血管生物学
- 再生医療
- 分子代謝
背景:
- 成熟した心臓は,心筋細胞の細胞サイクル終了とポリプロイド化により,再生能力が制限されています.
- 心筋細胞の代謝は産後変化し 再生能力の喪失と一致する.
- 再生性心筋細胞群の維持における代謝再プログラミングの役割は不明である.
研究 の 目的:
- 心臓の修復におけるRNA結合タンパク質 LIN28aの役割を調査する.
- LIN28aが再生可能な単核二倍体心筋細胞を維持できるかどうかを判断する.
- メタボリック再プログラムと 心臓の再生を関連付ける
主な方法:
- マウスモデルにおけるLIN28a過剰発現 (トランスジェネシス,新生児/成人細胞培養,心筋損傷モデル)
- 心筋細胞数,細胞サイクル状態,およびプロイディの評価
- LIN28a過剰発現する心筋細胞における代謝分析 (糖分分解,ATP生成,酵素濃度)
- LIN28aの標的を特定するためのRNA免疫沈殿配列.
主要な成果:
- 産後心臓におけるLIN28a過剰発現は,ポリプロイド化が減少し,心筋細胞循環活動が増加した.
- 若いマウスと大人のマウスの両方で,心臓の機能と生存率が向上した.
- LIN28aは心筋細胞における糖分分解とATP生成を増加させ,長時間非コーディングRNA- H19を主要標的として特定した.
- LIN28aまたはH19の抑制は,これらの補正効果を鈍化させた.
結論:
- LIN28aは心筋細胞の代謝を再プログラムし,単核二重細胞の持続を促進する.
- この代謝再プログラムにより 心臓の修復と機能が向上します
- LIN28aは,心筋細胞の代謝と,心臓の再生過程の調節を結びつけています.
関連する概念動画
Formation of Muscle Fibers from Myoblasts
5.1K
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
5.1K
lncRNA - Long Non-coding RNAs
8.8K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.8K
Regulation of Expression at Multiple Steps
976
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
976
Types of RNA
6.1K
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA Performs Diverse...
RNA Performs Diverse...
6.1K
Master Transcription Regulators
7.0K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.0K
Regulation of Expression Occurs at Multiple Steps
23.0K
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...
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...
23.0K


