The Clothes Make the mRNA: Past and Present Trends in mRNP Fashion

Abstract

Throughout their lifetimes, messenger RNAs (mRNAs) associate with proteins to form ribonucleoproteins (mRNPs). Since the discovery of the first mRNP component more than 40 years ago, what is known as the mRNA interactome now comprises >1,000 proteins. These proteins bind mRNAs in myriad ways with varying affinities and stoichiometries, with many assembling onto nascent RNAs in a highly ordered process during transcription and precursor mRNA (pre-mRNA) processing. The nonrandom distribution of major mRNP proteins observed in transcriptome-wide studies leads us to propose that mRNPs are organized into three major domains loosely corresponding to 5′ untranslated regions (UTRs), open reading frames, and 3′ UTRs. Moving from the nucleus to the cytoplasm, mRNPs undergo extensive remodeling as they are first acted upon by the nuclear pore complex and then by the ribosome. When not being actively translated, cytoplasmic mRNPs can assemble into large multi-mRNP assemblies or be permanently disassembled and degraded. In this review, we aim to give the reader a thorough understanding of past and current eukaryotic mRNP research.

Rules of RNA specificity of hnRNP A1 revealed by global and quantitative analysis of its affinity distribution

“…2E). Indeed, 1 H NMR of the imino region of 5′-GGUGACC-3′ and 5′-UGUGGCA-3′ (proposed pairing interactions underlined here and throughout remaining text) show new imino signals with chemical shifts consistent with GC and AU base pairs (Fig. S6).…”

“…hnRNP A1 | protein-RNA specificity | RNA structure | thermodynamics | binding kinetics G ene expression is regulated by an ensemble of protein-RNA complexes that assemble and disassemble throughout the lifetime of a transcript (1)(2)(3)(4)(5). Knowledge of the determinants of RNA-binding protein (RBP) specificity is therefore essential to understanding the relative affinity for sites of association within the transcriptome.…”

Evolutionarily Conserved Polyadenosine RNA Binding Protein Nab2 Cooperates with Splicing Machinery To Regulate the Fate of Pre-mRNA

“…Although much of this control occurs at the level of transcription, both co-and posttranscriptional events also play key regulatory roles. Newly synthesized mRNAs undergo numerous processing events, including 5= capping, splicing, 3=-end processing, and export to the cytoplasm (1,2). Ensuring the synchrony of mRNA biogenesis requires RNA binding proteins that not only perform the processing tasks but also couple the events to ensure that only properly processed mRNAs are available for translation in the cytoplasm (3).…”

“…Although steps in mRNA processing are often depicted and studied as separate events, there is a growing body of evidence that these processing events are intimately coupled to one another (2). For example, splicing and 3=-end processing are coupled in humans as mutations in splice site and polyadenylation consensus sequences mutually disrupt both splicing and polyadenylation (4)(5)(6).…”

A DEAD-box RNA helicase promotes thermodynamic equilibration of kinetically trapped RNA structures in vivo

“…Interactions with specific RNA-binding proteins and small ligands have also been shown to "capture" certain RNA conformations (Weeks and Cech 1996;Haller et al 2011). Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a large and diverse class of proteins that interact with RNA polymerase II transcripts in nuclei (Dreyfuss et al 1993;He and Smith 2009;Singh et al 2015). Many hnRNPs exhibit RNA chaperone activity in vitro and in vivo suggesting that cotranscriptional binding of hnRNPs might modulate assembly of stable RNA structures within nascent transcripts (Karpel et al 1982;Herschlag et al 1994;Belisova et al 2005).…”