RNA-protein interactions in human health and disease

Abstract

It is now clear that the genomes of many organisms encode thousands of large and small non-coding (nc)RNAs. However, relative to the discovery of ncRNAs the functions and mechanisms of ncRNAs remain disproportionately understood. One intriguing observation is that many ncRNAs are found to be associated with protein complexes including those involved in transcription regulation, post-transcriptional silencing, and epigentic regulation. These observations suggest that the functions and mechanisms of many of these ncRNAs may depend on their interactions with various protein complexes within the cell. In this review we discuss well known examples as well as newly emerging evidence of a widespread RNA-protein interactions in distinct biological processes in a wide range of organisms, and highlight the importance of developing new technologies to dissect these interactions. Finally, we propose that mis-regulation of ncRNAs interactions with their protein partners may contribute to human disease, and open up a novel approach to therapeutic interventions.

Fig 1. Extensive Large Non-coding RNA-protein Interactions in the Mammalian Genome Which are involved in Numerous Biological Processes

In the nucleus large non-coding RNAs interact with chromatin-modifying complexes (e.g., PRC2, CoREST, LSD1) and are thought to guide these complexes to their site of action and/or serve as scaffolds. Also, large non-coding RNAs play a crucial role in other processes such as splicing as well as nuclear-cytoplasmic shuttling. In the cytoplasm, large non-coding RNAs are also involved in several process including signal recognition particle (SRP) which directs nascent secretory proteins to the endoplasmic reticulum and some large non-coding RNAs have been found in P-bodies.