The organization and regulation of mRNA–protein complexes

Abstract

In a eukaryotic cell, each messenger RNA (mRNA) is bound to a variety of proteins to form an mRNA–protein complex (mRNP). Together, these proteins impact nearly every step in the life cycle of an mRNA and are critical for the proper control of gene expression. In the cytoplasm, for instance, mRNPs affect mRNA translatability and stability and provide regulation of specific transcripts as well as global, transcriptome‐wide control. mRNPs are complex, diverse, and dynamic, and so they have been a challenge to understand. But the advent of high‐throughput sequencing technology has heralded a new era in the study of mRNPs. Here, I will discuss general principles of cytoplasmic mRNP organization and regulation. Using microRNA‐mediated repression as a case study, I will focus on common themes in mRNPs and highlight the interplay between mRNP composition and posttranscriptional regulation. mRNPs are an important control point in regulating gene expression, and while the study of these fascinating complexes presents remaining challenges, recent advances provide a critical lens for deciphering gene regulation. WIREs RNA 2017, 8:e1369. doi: 10.1002/wrna.1369For further resources related to this article, please visit the WIREs website.

Codon usage and amino acid identity are major determinants of mRNA stability in humans

“…Mammalian mRNA half-lives vary extensively in vivo (Lugowski et al, 2018;Schwanhäusser et al, 2011), and a major question has been which processes and regulatory elements underlie this variation. In mammals, the 3' untranslated region (UTR) is a hotspot for regulation, containing the majority of instability-promoting sites, such as AU-rich elements or microRNA-binding sites (Bartel, 2009;Rissland, 2016;Shyu et al, 1989;Xu et al, 1998). Typically, instability-promoting motifs accelerate decay by eventually recruiting deadenylation-dependent decay machinery and stripping stabilizing mRNP components (Eulalio et al, 2009;Fabian et al, 2011;2009;Kuzuoğlu-Öztürk et al, 2016;Rissland et al, 2017;Zekri et al, 2013) We have previously demonstrated that codon usage is a key mechanism underlying mRNA half-life variability in S. cerevisiae such that changes in overall "optimal" and "non-optimal" synonymous codon composition manifest as dramatic changes in mRNA stability (Presnyak et al, 2015;.…”

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

“…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.…”

Elucidating the mechanism of miRNA-214 in the regulation of gingival carcinoma

“…It has recently been demonstrated that a class of small, endogenous and non-coding nucleic acid miRNAs are able to prevent transcription of PTEN mRNA (45). According to the current literature, miRNAs have a high level of stability in conventional, formalin-fixed, paraffin-embedded clinical tissue specimens, which suggests that they may have potential as diagnostic molecular markers; however, mRNAs tend to be more susceptible to environmental impact and are more unstable than miRNAs (46)(47)(48). Furthermore, it has previously been suggested that miRNAs serve important roles in tumorigenesis via their regulation of protein coding genes (49,50).…”