小柯机器人

近日，瑞典卡洛琳卡学院Rickard Sandberg团队揭示长非编码RNA的转录动力学和分子功能。这一研究成果于2022年3月3日在线发表在国际学术期刊《自然—遗传学》上。

研究人员使用等位基因敏感的单细胞RNA测序证明，与信使RNA相比，长非编码RNA（lncRNA）在两次转录爆发之间的持续时间是两倍。此外，研究人员观察到由于低频率的突发产生了更多的RNA分子，细胞间的变异性增加。利用异步生长的细胞的异质性，研究人员发现并通过实验验证了具有细胞状态特异性功能的lncRNA，这些功能涉及细胞周期的进展和细胞凋亡。

最后，研究人员确定了顺式功能的lncRNA，并表明敲除这些lncRNA可以调节附近蛋白编码基因的转录突发频率或大小。总之，研究人员确定了不同的lncRNA转录调控，并证明了lncRNA在mRNA转录爆发调控中的作用。

据了解，越来越多的lncRNA的功能已被实验证实，但对它们的转录动态却知之甚少，确定它们的调控作用也很有挑战性。

附：英文原文

Title: Transcriptional kinetics and molecular functions of long noncoding RNAs

Author: Johnsson, Per, Ziegenhain, Christoph, Hartmanis, Leonard, Hendriks, Gert-Jan, Hagemann-Jensen, Michael, Reinius, Bjrn, Sandberg, Rickard

Issue&Volume: 2022-03-03

Abstract: An increasing number of long noncoding RNAs (lncRNAs) have experimentally confirmed functions, yet little is known about their transcriptional dynamics and it is challenging to determine their regulatory effects. Here, we used allele-sensitive single-cell RNA sequencing to demonstrate that, compared to messenger RNAs, lncRNAs have twice as long duration between two transcriptional bursts. Additionally, we observed increased cell-to-cell variability in lncRNA expression due to lower frequency bursting producing larger numbers of RNA molecules. Exploiting heterogeneity in asynchronously growing cells, we identified and experimentally validated lncRNAs with cell state-specific functions involved in cell cycle progression and apoptosis. Finally, we identified cis-functioning lncRNAs and showed that knockdown of these lncRNAs modulated the nearby protein-coding gene’s transcriptional burst frequency or size. In summary, we identified distinct transcriptional regulation of lncRNAs and demonstrated a role for lncRNAs in the regulation of mRNA transcriptional bursting.

DOI: 10.1038/s41588-022-01014-1

Source: https://www.nature.com/articles/s41588-022-01014-1

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