RNA modifications and structures cooperate to guide RNA–protein interactions

Abstract

An emerging body of evidence indicates that post-transcriptional gene regulation not only relies on the linear sequence of messenger RNAs but also on their folding into intricate secondary structures and on chemical modification of the RNA bases. These features, which are highly dynamic and interdependent, exert direct control over the transcriptome thereby influencing many aspects of cell function. Here, we consider that coupling of RNA modifications and structure actively shapes RNA-protein interactions through individual steps of gene expression.

Fingerprints of Modified RNA Bases from Deep Sequencing Profiles

“…11 The field is rapidly moving as more modifications are found in mRNAs, and as the pathways that recognize, add, and remove modifications are identified. 12–14 …”

Untitled

“…In a crawling flow and neglecting hydrodynamic interactions, the drag force is taken as Stokes drag on a sphere and it can be defined as (35) Where ∑ is the dog coefficient and u ∞ (ri) is the unperturbed velocity of the solvent evaluated at the position of the particle. The motion governing differential equation of the particle becomes as (36) and is known as Langevin equation, where {ri} is the set of all partials positions on which nonhydrodynamic force depends.…”

“…The post-transcriptional gene regulation depends not only on the mRNAs sequence but also on their folding into complex secondary structures and chemical modifications of RNA bases. These features of RNA are highly dynamic and independent and having their direct control in the transcriptome, which leads changes in several functions of the cell 35 . Hence, it is important to analyze the coupling of RNA structures and its modifications and RNA-protein interactions at different steps of the gene expression process 36 .…”

Deregulation of RNA Metabolism in Microsatellite Expansion Diseases

“…The typical pre-mRNA processing events comprise 5’ capping, splicing, and 3’ polyadenylation, which are directly linked to the nucleo-cytoplasmic export and eventual fate of mRNAs. RNA Binding Proteins (RBPs) are essential in carrying out these processing events in both the nucleus and cytoplasm by interacting with RNA sequence or structural elements and forming distinct mRNA-protein (mRNP) complexes [2]. Disruption of RBP function(s), therefore, frequently results in deleterious RNA metabolism defects that in some cases become pathogenic [3, 4].…”