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微RNA-198和FSTL1的"看看"表达来自伤口愈合中的单个转录
Gopinath M Sundaram1, John E A Common, Felicia E Gopal
1Institute of Medical Biology, Agency for Science Technology & Research (A*STAR), 138648, Singapore.
Nature
|February 12, 2013
概括
一个新的转录后开关在伤口愈合期间调节基因表达. 这种开关控制了微RNA-198和folistatin-like 1的表达,这对角质细胞迁移和组织修复至关重要,对糖尿病有影响.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 伤口愈合生物学 伤口愈合生物学
背景情况:
- 转录后调节允许动态的基因表达.
- 微RNA (miRNA) 和蛋白质可以从单个转录生成.
- 伤口愈合涉及复杂的细胞反应和基因表达变化.
研究的目的:
- 为了识别和描述一种控制基因表达的新型后转录开关.
- 阐明调节microRNA-198 (miR-198) 和follistatin-like 1 (FSTL1) 的时空表达的机制.
- 研究这种开关在角质细胞迁移和伤口再上皮质化中的作用.
主要方法:
- 利用人类的ex vivo器官培养系统来研究受伤时的基因表达变化.
- 研究了KH型拼接调节蛋白 (KSRP) 在转录处理和miRNA生物发生中的作用.
- 通过体外试验分析了FSTL1和miR-198对角质细胞迁移的影响.
- 在慢性糖尿病中检查基因表达模式.
主要成果:
- 发现了一个开关,在这个开关中,伤害通过降低 miR-198.8 的调节来促进 FSTL1 蛋白质的表达.
- 确定了KSRP作为一种关键的调节器,与主转录结合,决定了miR-198的处理.
- 证明FSTL1促进了角质细胞迁移,而miR-198通过准DIAPH1,PLAU和LAMC2来抑制它.
- 在不治愈的糖尿病中观察到持续的miR-198和缺席的FSTL1,与未能治愈的伤口相关.
结论:
- 一个涉及miR-198和FSTL1的新型后转录调节开关协调了伤口再上皮化.
- 这种由KSRP和TGF-β信号传递介导的开关确保了特定环境的基因表达,以有效地修复组织.
- 这种开关的调节失调有助于慢性糖尿病的愈合受损.
相关概念视频
MicroRNAs
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 ends...
MicroRNAs
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...
MicroRNAs
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 ends...
Regulation of Expression at Multiple Steps
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 addition of a...
Small interfering RNAs (siRNA)
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
