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Updated: May 14, 2025

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CRISPRi屏幕揭示了人类单细胞生长的 lncRNA 调节器

Cristina Flores-Arena¹, Eric Malekos², Christy Montano¹

¹Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, California, USA.

The Journal of biological chemistry

|May 9, 2025

概括

高通量查确定了两个长非编码RNA (lncRNAs),LNCRMP和OLMALINC,这对人类单细胞活力至关重要. 它们的抑制通过影响分别亡和细胞循环途径来限制增殖.

科学领域:

分子生物学分子生物学
遗传学遗传学是一个
免疫学免疫学免疫学

背景情况:

长非编码RNAs (lncRNAs) 是生物过程的关键调节者,但它们的大多数功能仍然未知.
人类基因组中注释了超过36,000个lncRNA,为功能性发现提供了一个广的景观.

研究的目的:

通过使用高通量查来识别对人类单细胞活力至关重要的功能性 lncRNA.
描述新发现的lncRNAs在单细胞增殖和相关途径中的作用.

主要方法:

在THP1人类单细胞细胞系中进行了高通量CRISPR干扰 (CRISPRi) 屏幕.
通过基因抑制和RNA测序验证和表征顶级lncRNA候选物,包括LNCRMP和OLMALINC.

主要成果:

鉴定出38个对单细胞活力至关重要的 lncRNA.
抑制LNCRMP和OLMALINC显著损害了THP1细胞的增殖.
抑制LNCRMP影响了亲细胞突变通路,而抑制OLMALINC影响了细胞循环相关基因.

结论:

在cis中,LNCRMP和OLMALINC的功能是调节对单细胞生长至关重要的邻近基因.
高通量查是一种有效的方法,用于发现与细胞活力相关的功能 lncRNA.
这项研究揭示了lncRNAs在调节单细胞增殖和存活中的新角色.

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相关概念视频

lncRNA - Long Non-coding RNAs

lncRNA - Long Non-coding RNAs

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...