Somasundaram Kumaravel, Gupta Bhavana, Jain Nishkarsh, Jana Samarjit
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
Front Genet. 2022 Aug 10;13:930792. doi: 10.3389/fgene.2022.930792. eCollection 2022.
Most of the human genome, except for a small region that transcribes protein-coding RNAs, was considered junk. With the advent of RNA sequencing technology, we know that much of the genome codes for RNAs with no protein-coding potential. Long non-coding RNAs (lncRNAs) that form a significant proportion are dynamically expressed and play diverse roles in physiological and pathological processes. Precise spatiotemporal control of their expression is essential to carry out various biochemical reactions inside the cell. Intracellular organelles with membrane-bound compartments are known for creating an independent internal environment for carrying out specific functions. The formation of membrane-free ribonucleoprotein condensates resulting in intracellular compartments is documented in recent times to execute specialized tasks such as DNA replication and repair, chromatin remodeling, transcription, and mRNA splicing. These liquid compartments, called membrane-less organelles (MLOs), are formed by liquid-liquid phase separation (LLPS), selectively partitioning a specific set of macromolecules from others. While RNA binding proteins (RBPs) with low complexity regions (LCRs) appear to play an essential role in this process, the role of RNAs is not well-understood. It appears that short nonspecific RNAs keep the RBPs in a soluble state, while longer RNAs with unique secondary structures promote LLPS formation by specifically binding to RBPs. This review will update the current understanding of phase separation, physio-chemical nature and composition of condensates, regulation of phase separation, the role of lncRNA in the phase separation process, and the relevance to cancer development and progression.
除了一小部分转录蛋白质编码RNA的区域外，人类基因组的大部分曾被认为是无用的。随着RNA测序技术的出现，我们现在知道基因组的许多部分编码的是没有蛋白质编码潜力的RNA。占相当比例的长链非编码RNA（lncRNA）动态表达，并在生理和病理过程中发挥多种作用。其表达的精确时空控制对于在细胞内进行各种生化反应至关重要。具有膜结合区室的细胞内细胞器以创造独立的内部环境来执行特定功能而闻名。近年来有文献记载，无膜核糖核蛋白凝聚物的形成会产生细胞内区室，以执行诸如DNA复制和修复、染色质重塑、转录和mRNA剪接等专门任务。这些液滴区室，即无膜细胞器（MLO），是通过液-液相分离（LLPS）形成的，能从其他分子中选择性地分离出一组特定的大分子。虽然具有低复杂性区域（LCR）的RNA结合蛋白（RBP）似乎在这一过程中起着至关重要的作用，但RNA的作用尚未得到很好的理解。似乎短的非特异性RNA能使RBP保持可溶状态，而具有独特二级结构的较长RNA则通过与RBP特异性结合来促进LLPS的形成。本综述将更新对相分离、凝聚物的物理化学性质和组成、相分离的调控、lncRNA在相分离过程中的作用以及与癌症发生和发展的相关性的当前认识。
