Abstract

Functional specialization of cells and tissues in metazoans require specific gene expression patterns. Biological processes, thus, need precise temporal and spatial coordination of gene activity. Regulation of the fate of messenger RNA plays a crucial role in this context. In the present review, the current knowledge related to the role of RNA-binding proteins in the whole mRNA life-cycle is summarized. This field opens up a new angle for understanding the importance of the post-transcriptional control of gene expression in cancer cells. The emerging role of non-classic RNA-binding proteins is highlighted. The goal of this review is to encourage readers to view, through the mRNA life-cycle, novel aspects of the molecular basis of cancer and the potential to develop RNA-based therapies.

Highlights

  • Introduction to the MessengerRNA Life-CycleRegulation of eukaryotic gene expression is crucial in pathophysiological responses to extracellular and intracellular signals in the context of homeostasis maintenance and cellular differentiation or in stress response and cell survival

  • Competition between binding sites and/or between RNA-Binding Proteins (RBPs) allows, from a single gene, the production of several variants resulting from the use of 5 and 3 alternative splicing sites, intron retention, or exon skipping. These RBP-binding site sequences are called exonic splicing enhancers (ESE) or exonic splicing silencers (ESS) and intronic splicing enhancers (ISE) or intronic splicing silencers (ISS). These motifs are recognized by Serine/Arginine-rich (SR) proteins or heterogeneous nuclear ribonucleoproteins, which activate or inhibit the splicing process by affecting the spliceosome assembly [57,58]

  • Downregulation of AU rich elements (AREs)-BPs is observed in cancers, leading to stabilization of messenger RNA (mRNA) targets involved in the cell cycle, in angiogenesis (VEGF, for example), or in apoptotic resistance (BCL2, for example)

Read more

Summary

Major Actors of the mRNA Life-Cycle

Transcription is the first step of gene expression and involves RNA biosynthesis. From the early beginning of their transcription until they are degraded, most RNA molecules are constantly associated with proteins in cells. The RNA-binding motif itself is short, usually between 4 to 6 nucleotides It can be even shorter and restricted to a single nucleotide, as in the case of PUF domain (comprised of the Pumilio and FBF homology protein). T2a0r1g8e, t1s9i,n65a0specific manner [3] Another criterion has to be taken into consideration to understand RBP properties: it is the presence of additional protein regions working as RNA-chaperones (by helping the initially single-stranded RNA to form various secondary or tertiary structures), enzymes (such as helicase, ribonuclease, endonuclease, or telomerase), or assembling proteins [3,4]. Sci. 2018, 19, 650 binds double-stranded DNA, forming a large group of DNA-binding and RNA-binding proteins (DRBPs) These DRBPs are thought to regulate large subsets of genes involved in broad cceelllluullaarrpprorcoecsessesse,si,ncinlucdluindgintgrantrsacrnispctrioipnt,iotrna,nstlraatniosnla,tgioen,e sgielennecisnigle, nDcNinAg,daDmNaAgedreasmpoangsee,rteeslpoomnesree, mtealoinmtenreanmcaei,natpeonpatnocsei,s,aapnodptroessips,oannsdesrteospexotnrseems etoteemxtpremraetutreems p[2e8r]a.tures [28]. Future perspective lies in the production of engineering synthetic RNAs for therapeutic use

Co-Transcriptional Processes in the mRNA Life-Cycle
Pre-mRNA Splicing
Nuclear Export
Factors Modulating mRNA Stability
Non-Coding RNAs and RNA Editing
Cytoplasmic Granules
Therapeutic Approaches Targeting RBPs and Related mRNA
Which Targets?
Which Tools?
Findings
Conclusions and Take-Home Messages
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.