Abstract
Alteration of RNA structure by environmental signals is a fundamental mechanism of gene regulation. For example, the riboswitch is a noncoding RNA regulatory element that binds a small molecule and causes a structural change in the RNA, thereby regulating transcription, splicing, or translation of an mRNA. The role of riboswitches in metabolite sensing and gene regulation in bacteria and other lower species was reported almost two decades ago, but riboswitches have not yet been discovered in mammals. An analog of the riboswitch, the protein-directed RNA switch (PDRS), has been identified as an important regulatory mechanism of gene expression in mammalian cells. RNA-binding proteins and microRNAs are two major executors of PDRS via their interaction with target transcripts in mammals. These protein-RNA interactions influence cellular functions by integrating environmental signals and intracellular pathways from disparate stimuli to modulate stability or translation of specific mRNAs. The discovery of a riboswitch in eukaryotes that is composed of a single class of thiamine pyrophosphate (TPP) suggests that additional ligand-sensing RNAs may be present to control eukaryotic or mammalian gene expression. In this review, we focus on protein-directed RNA switch mechanisms in mammals. We offer perspectives on the potential discovery of mammalian protein-directed and compound-dependent RNA switches that are related to human disease and medicine.
Highlights
Alteration of Ribonucleic acid (RNA) structure by environmental signals is a fundamental mechanism of gene regulation
We focus on mammalian protein-directed RNA switch mechanisms and provide perspectives on potential PDRSs and riboswitch-like RNA switches in mammals
Translational regulation by heterogeneous nuclear ribonucleoproteins (hnRNPs) L via potential competition between hnRNP L and miRNA binding was observed for a cohort of target mRNA 30untranslated region (30UTR) in Hela cells [40]. These findings suggest that hnRNP L-directed human RNA switches are broadly present across multiple cell types
Summary
Ribonucleic acid (RNA) plays a versatile role in translating genetic codon information from DNA genomes into functional proteins for living organisms. The riboswitch is an RNA regulatory element of a corresponding mRNA It binds to a small molecule and causes a structural change in the RNA, independent of protein binding, thereby regulating mRNA transcription, splicing, or translation [1]. The RNA ‘‘aptamer” is a structural element generally situated in the 5’UTR of the regulated mRNA, and is a biosensor for direct binding of the ligand Upon ligand binding, this RNA aptamer induces a conformational change immediately downstream, in a region of the RNA called the ‘‘expression platform”. Posttranscriptional modification of N(6)-methyladenosine in mRNAs disrupts the Watson-Crick base pair of A-U and increases the binding affinity of hnRNP C to its target mRNAs [27] These RNA-protein interactions integrate environmental or intracellular signals from disparate stimulatory conditions to regulate gene expression at the post-transcriptional level and alter cellular function. We speculate that metabolic enzymes, ribosomes, and pathogenic and pharmacological small molecules drive these hypothetical mammalian RNA switches, which may modulate metabolic homeostasis, disease progression, and beneficial or side effects of drugs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callMore From: Computational and Structural Biotechnology Journal
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.
