A birth‐to‐death view of mRNA from the RNA recognition motif perspective

Abstract

RNA binding proteins are a large and varied group of factors that are the driving force behind post-transcriptional gene regulation. By analogy with transcription factors, RNA binding proteins bind to various regions of the mRNAs that they regulate, usually upstream or downstream from the coding region, and modulate one of the five major processes in mRNA metabolism: splicing, polyadenylation, export, translation and decay. The most abundant RNA binding protein domain is called the RNA Recognition Motif (RRM) 1 . It is probably safe to say that an RRM-containing protein is making some contact with an mRNA throughout its existence. The transcriptional counterpart would likely be the histones, yet the multitude of specific functions that are results of RRM based interactions belies the universality of the motif. This complex and diverse application of a single protein motif was used as the basis to develop an advanced graduate level seminar course in RNA:protein interactions. The course, utilizing a learner-centered empowerment model, was developed to dissect each step in RNA metabolism from the perspective of an RRM containing protein. This provided a framework to discuss the development of specificity for the RRM for each required process.Keywords: RNA recognition motif, splicing, RNA export, translation, polyadenylation, mRNA localization, mRNA decay.A wide range of proteins are able to associate with mRNA via highly conserved RNA-binding domains and play a pivotal role in mRNA metabolism and hence, in the post-transcriptional regulation of gene expression. The RNA recognition motif (RRM), alternatively is one of the most abundant eukaryotic protein domains that mediate interaction between mRNAs and proteins. The pFAM database currently lists over 12,000 sequences containing RRM motifs derived from over 400 species [1]. In humans there are 500 RRM-containing proteins annotated, suggesting that 2% of the genome is dedicated to RRM production. The observation that precursor mRNAs and nuclear mRNAs are almost always found complexed with proteins led to the initial detection of RRMs 20 years ago [2]. Since then, RRM containing proteins have been extensively studied in conjunction with their function in the development of RNA and gene expression [3][4][5]. The RRM comprises a consensus RNAbinding sequence about 75-85 amino acids long, located at N-termini of proteins, the structure of which is a b 1 a 1 b 2 b 3 a 2 b 4 fold [6]. RNA-binding protein motifs are functionally conserved between eukaryotes and prokaryotes and often bind other proteins in addition to RNA [7]. Here we review the function of several RRM-containing proteins that are crucial to the process of RNA metabolism from transcription through decay highlighting specific proteins involved at each stage. Figure 1 illustrates the life-cycle of an mRNA making note of the RRM-containing proteins discussed below. mRNA SPLICINGThe spliceosome is an intricate organization of protein/ RNA complexes whose primary purpose is to remove introns from pre-mRNA. Accur...

Human DND1‐RRM2 forms a non‐canonical domain swapped dimer

“…They modulate several major processes in mRNA metabolism, which are; capping, splicing, polyadenylation, export, translation, and decay. 2 Nuances in interaction affinity is mediated by RNA binding domain structure, RNA structure, auxiliary protein interaction, PTM based regulation, and so forth. RRMs with their varied types of interactions with proteins/nucleic acids happen to be highly functionally versatile.…”

“…RRMs are essential in regulating post‐transcriptional gene regulation by virtue of their interactions. They modulate several major processes in mRNA metabolism, which are; capping, splicing, polyadenylation, export, translation, and decay 2 . Nuances in interaction affinity is mediated by RNA binding domain structure, RNA structure, auxiliary protein interaction, PTM based regulation, and so forth.…”