RNA Sensing in Cells: An Update of Its Mechanisms, Disorders and Therapeutics

Abstract

The workhorses of a cell are the protein-coding RNA and the non-coding RNA (ncRNA). Many of these RNAs and the RNA-binding proteins that are linked to them, known as ribonucleoprotein complexes (RNPs), are essential for cellular processes. Accurate production of many protein-coding RNAs (messenger RNAs [mRNAs]) and (noncoding RNAs[ncRNAs]) is essential for cells to function where they carry out functions such as translation, transcription, and RNA processing. These process require high fidelity due to the abundance of RNA-binding proteins and due to cellular insults both endogenous and exogenous in the form of pathogens, chemicals, and physiological stimuli. The ability of cells to recognize and respond to the presence of RNA, to trigger biological reactions, is known as RNA sensing. The mechanism is essential for controlling gene expression and cell survival in prokaryotes and eukaryotes. In eukaryotes, they enable identifying pathogens—especially viruses—and initiate antiviral defenses. The current review covers RNA sensing in several aspects, such as importance of RNA, RNA sensing receptors, signaling pathways, and aberrant RNA pathways.  An additional overview of diseases, therapeutic applications along with future perspectives is covered. With advances in genomics and annotation methods, the focus globally has shifted to RNA and its roles in cellular biology. Further, the annotation of the human genome has yielded insights into the functional roles of junk DNA and RNA. The review in part highlights these developments in the area of RNA sensing. Further, since RNA sensing has numerous applications in fundamental biology, biotechnology, and also in the form of programmable RNA in medicine, its significance across disciplines emphasizes its value.