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Cell Death and Differentiation Jan 2015Since their discovery 20 years ago, miRNAs have attracted much attention from all areas of biology. These short (∼22 nt) non-coding RNA molecules are highly... (Review)
Review
Since their discovery 20 years ago, miRNAs have attracted much attention from all areas of biology. These short (∼22 nt) non-coding RNA molecules are highly conserved in evolution and are present in nearly all eukaryotes. They have critical roles in virtually every cellular process, particularly determination of cell fate in development and regulation of the cell cycle. Although it has long been known that miRNAs bind to mRNAs to trigger translational repression and degradation, there had been much debate regarding their precise mode of action. It is now believed that translational control is the primary event, only later followed by mRNA destabilisation. This review will discuss the most recent advances in our understanding of the molecular underpinnings of miRNA-mediated repression. Moreover, we highlight the multitude of regulatory mechanisms that modulate miRNA function.
Topics: Animals; Cell Cycle; Eukaryota; Evolution, Molecular; Humans; MicroRNAs; Protein Biosynthesis; RNA Stability; RNA, Messenger
PubMed: 25190144
DOI: 10.1038/cdd.2014.112 -
Wiley Interdisciplinary Reviews. RNA 2013Staufen1 (STAU1)-mediated mRNA decay (SMD) is an mRNA degradation process in mammalian cells that is mediated by the binding of STAU1 to a STAU1-binding site (SBS)... (Review)
Review
Staufen1 (STAU1)-mediated mRNA decay (SMD) is an mRNA degradation process in mammalian cells that is mediated by the binding of STAU1 to a STAU1-binding site (SBS) within the 3'-untranslated region (3'-UTR) of target mRNAs. During SMD, STAU1, a double-stranded (ds) RNA-binding protein, recognizes dsRNA structures formed either by intramolecular base pairing of 3'-UTR sequences or by intermolecular base pairing of 3'-UTR sequences with a long-noncoding RNA (lncRNA) via partially complementary Alu elements. Recently, STAU2, a paralog of STAU1, has also been reported to mediate SMD. Both STAU1 and STAU2 interact directly with the ATP-dependent RNA helicase UPF1, a key SMD factor, enhancing its helicase activity to promote effective SMD. Moreover, STAU1 and STAU2 form homodimeric and heterodimeric interactions via domain-swapping. Because both SMD and the mechanistically related nonsense-mediated mRNA decay (NMD) employ UPF1; SMD and NMD are competitive pathways. Competition contributes to cellular differentiation processes, such as myogenesis and adipogenesis, placing SMD at the heart of various physiologically important mechanisms.
Topics: Animals; Cell Differentiation; Gene Expression Regulation; Humans; Mammals; RNA Stability; RNA-Binding Proteins
PubMed: 23681777
DOI: 10.1002/wrna.1168 -
Nucleic Acids Research Oct 2020The nuclear Cap-Binding Complex (CBC), consisting of Nuclear Cap-Binding Protein 1 (NCBP1) and 2 (NCBP2), associates with the nascent 5'cap of RNA polymerase II...
The nuclear Cap-Binding Complex (CBC), consisting of Nuclear Cap-Binding Protein 1 (NCBP1) and 2 (NCBP2), associates with the nascent 5'cap of RNA polymerase II transcripts and impacts RNA fate decisions. Recently, the C17orf85 protein, also called NCBP3, was suggested to form an alternative CBC by replacing NCBP2. However, applying protein-protein interaction screening of NCBP1, 2 and 3, we find that the interaction profile of NCBP3 is distinct. Whereas NCBP1 and 2 identify known CBC interactors, NCBP3 primarily interacts with components of the Exon Junction Complex (EJC) and the TRanscription and EXport (TREX) complex. NCBP3-EJC association in vitro and in vivo requires EJC core integrity and the in vivo RNA binding profiles of EJC and NCBP3 overlap. We further show that NCBP3 competes with the RNA degradation factor ZC3H18 for binding CBC-bound transcripts, and that NCBP3 positively impacts the nuclear export of polyadenylated RNAs and the expression of large multi-exonic transcripts. Collectively, our results place NCBP3 with the EJC and TREX complexes in supporting mRNA expression.
Topics: Active Transport, Cell Nucleus; Cell Nucleus; Exons; Gene Expression Regulation; Humans; Nuclear Cap-Binding Protein Complex; RNA; RNA Cap-Binding Proteins; RNA Polymerase II; RNA Stability; RNA Transport; RNA, Messenger; RNA-Binding Proteins; Transcription Factors; Transcription, Genetic
PubMed: 32960271
DOI: 10.1093/nar/gkaa744 -
Viruses Jan 2017The innate immune system has evolved a number of sensors that recognize viral RNA (vRNA) to restrict infection, yet the full spectrum of host-encoded RNA binding... (Review)
Review
The innate immune system has evolved a number of sensors that recognize viral RNA (vRNA) to restrict infection, yet the full spectrum of host-encoded RNA binding proteins that target these foreign RNAs is still unknown. The RNA decay machinery, which uses exonucleases to degrade aberrant RNAs largely from the 5' or 3' end, is increasingly recognized as playing an important role in antiviral defense. The 5' degradation pathway can directly target viral messenger RNA (mRNA) for degradation, as well as indirectly attenuate replication by limiting specific pools of endogenous RNAs. The 3' degradation machinery (RNA exosome) is emerging as a downstream effector of a diverse array of vRNA sensors. This review discusses our current understanding of the roles of the RNA decay machinery in controlling viral infection.
Topics: Humans; Immunity, Innate; RNA Stability; RNA Viruses; RNA, Viral
PubMed: 28054965
DOI: 10.3390/v9010002 -
Essays in Biochemistry Apr 2018In contrast to the cyanobacterial ancestor, chloroplast gene expression is predominantly governed on the post-transcriptional level such as modifications of the RNA... (Review)
Review
In contrast to the cyanobacterial ancestor, chloroplast gene expression is predominantly governed on the post-transcriptional level such as modifications of the RNA sequence, decay rates, exo- and endonucleolytic processing as well as translational events. The concerted function of numerous chloroplast RNA-binding proteins plays a fundamental and often essential role in all these processes but our understanding of their impact in regulation of RNA degradation is only at the beginning. Moreover, metabolic processes and post-translational modifications are thought to affect the function of RNA protectors. These protectors contain a variety of different RNA-recognition motifs, which often appear as multiple repeats. They are required for normal plant growth and development as well as diverse stress responses and acclimation processes. Interestingly, most of the protectors are plant specific which reflects a fast-evolving RNA metabolism in chloroplasts congruent with the diverging RNA targets. Here, we mainly focused on the characteristics of known chloroplast RNA-binding proteins that protect exonuclease-sensitive sites in chloroplasts of vascular plants.
Topics: Chloroplasts; Exonucleases; Plant Proteins; Plants; Protein Biosynthesis; RNA Stability; RNA, Plant; RNA-Binding Proteins; Stress, Physiological
PubMed: 29453323
DOI: 10.1042/EBC20170061 -
RNA (New York, N.Y.) Apr 2020Transcription initiation and RNA processing govern gene expression and enable bacterial adaptation by reshaping the RNA landscape. The aim of this study was to...
Transcription initiation and RNA processing govern gene expression and enable bacterial adaptation by reshaping the RNA landscape. The aim of this study was to simultaneously observe these two fundamental processes in a transcriptome responding to an environmental signal. A controlled σ system in was coupled to our previously described tagRNA-seq method to yield process kinetics information. Changes in transcription initiation frequencies (TIF) and RNA processing frequencies (PF) were followed using 5' RNA tags. Changes in TIF showed a binary increased/decreased pattern that alternated between transcriptionally activated and repressed promoters, providing the bacterial population with transcriptional oscillation. PF variation fell into three categories of cleavage activity: (i) constant and independent of RNA levels, (ii) increased once RNA has accumulated, and (iii) positively correlated to changes in TIF. This work provides a comprehensive and dynamic view of major events leading to transcriptomic reshaping during bacterial adaptation. It unveils an interplay between transcription initiation and the activity of specific RNA cleavage sites. This study utilized a well-known genetic system to analyze fundamental processes and can serve as a blueprint for comprehensive studies that exploit the RNA metabolism to decipher and understand bacterial gene expression control.
Topics: Adaptation, Physiological; Escherichia coli; RNA; RNA Processing, Post-Transcriptional; RNA Stability; RNA, Bacterial; Transcription Initiation, Genetic
PubMed: 31992590
DOI: 10.1261/rna.073288.119 -
Current Opinion in Structural Biology Feb 2016Cells contain powerful RNA decay machinery to eliminate unneeded RNA from the cell, and this process is an important and regulated part of controlling gene expression.... (Review)
Review
Cells contain powerful RNA decay machinery to eliminate unneeded RNA from the cell, and this process is an important and regulated part of controlling gene expression. However, certain structured RNAs have been found that can robustly resist degradation and extend the lifetime of an RNA. In this review, we present three RNA structures that use a specific three-dimensional fold to provide protection from RNA degradation, and discuss how the recently-solved structures of these RNAs explain their function. Specifically, we describe the Xrn1-resistant RNAs from arthropod-borne flaviviruses, exosome-resistant long non-coding RNAs associated with lung cancer metastasis and found in Kaposi's sarcoma-associated herpesvirus, and tRNA-like sequences occurring in certain plant viruses. These three structures reveal three different mechanisms to protect RNAs from decay and suggest RNA structure-based nuclease resistance may be a widespread mechanism of regulation.
Topics: Animals; Exonucleases; Humans; Nucleic Acid Conformation; RNA; RNA Stability; RNA, Transfer; RNA, Viral; Structure-Activity Relationship
PubMed: 26797676
DOI: 10.1016/j.sbi.2015.12.006 -
Epigenomics Feb 2020This review aims to systematically describe the biogenesis and degradation of circular RNAs (circRNAs), discusses the major functions of circRNAs, introduces the...
This review aims to systematically describe the biogenesis and degradation of circular RNAs (circRNAs), discusses the major functions of circRNAs, introduces the mechanisms by which circRNAs play a role in cancer, comprehensively summarize the relationship between circRNAs and anticarcinogen resistance as well as underlying specific mechanisms in multiple cancers. We screened and analyzed large quantity of scientific papers which associated with circRNAs, noncoding RNAs, function, cancer, drug resistance and chemoresistance, and then summarized in Figures 1 & 2 & Table 1. The biogenesis, degradation and function of circRNAs are specially compared with other noncoding RNAs, it can affect cancer pathogenesis and progression and are implicated in mediating resistance to various anticarcinogens in various types of cancer.
Topics: Anticarcinogenic Agents; Drug Resistance, Neoplasm; Humans; RNA Stability; RNA, Circular; Transcription, Genetic
PubMed: 31808351
DOI: 10.2217/epi-2019-0295 -
Biochimica Et Biophysica Acta 2013Messenger RNA degradation is a fundamental cellular process that plays a critical role in regulating gene expression by controlling both the quality and the abundance of... (Review)
Review
Messenger RNA degradation is a fundamental cellular process that plays a critical role in regulating gene expression by controlling both the quality and the abundance of mRNAs in cells. Naturally, viruses must successfully interface with the robust cellular RNA degradation machinery to achieve an optimal balance between viral and cellular gene expression and establish a productive infection in the host. In the past several years, studies have discovered many elegant strategies that viruses have evolved to circumvent the cellular RNA degradation machinery, ranging from disarming the RNA decay pathways and co-opting the factors governing cellular mRNA stability to promoting host mRNA degradation that facilitates selective viral gene expression and alters the dynamics of host-pathogen interaction. This review summarizes the current knowledge of the multifaceted interaction between viruses and cellular mRNA degradation machinery to provide an insight into the regulatory mechanisms that influence gene expression in viral infections. This article is part of a Special Issue entitled: RNA Decay mechanisms.
Topics: Endonucleases; Exoribonucleases; Gene Expression Regulation, Viral; Host-Pathogen Interactions; Humans; Infections; RNA Stability; RNA, Messenger; Viruses
PubMed: 23274304
DOI: 10.1016/j.bbagrm.2012.12.003 -
FEMS Microbiology Reviews Sep 2010The continuous degradation and synthesis of prokaryotic mRNAs not only give rise to the metabolic changes that are required as cells grow and divide but also rapid... (Review)
Review
The continuous degradation and synthesis of prokaryotic mRNAs not only give rise to the metabolic changes that are required as cells grow and divide but also rapid adaptation to new environmental conditions. In bacteria, RNAs can be degraded by mechanisms that act independently, but in parallel, and that target different sites with different efficiencies. The accessibility of sites for degradation depends on several factors, including RNA higher-order structure, protection by translating ribosomes and polyadenylation status. Furthermore, RNA degradation mechanisms have shown to be determinant for the post-transcriptional control of gene expression. RNases mediate the processing, decay and quality control of RNA. RNases can be divided into endonucleases that cleave the RNA internally or exonucleases that cleave the RNA from one of the extremities. Just in Escherichia coli there are >20 different RNases. RNase E is a single-strand-specific endonuclease critical for mRNA decay in E. coli. The enzyme interacts with the exonuclease polynucleotide phosphorylase (PNPase), enolase and RNA helicase B (RhlB) to form the degradosome. However, in Bacillus subtilis, this enzyme is absent, but it has other main endonucleases such as RNase J1 and RNase III. RNase III cleaves double-stranded RNA and family members are involved in RNA interference in eukaryotes. RNase II family members are ubiquitous exonucleases, and in eukaryotes, they can act as the catalytic subunit of the exosome. RNases act in different pathways to execute the maturation of rRNAs and tRNAs, and intervene in the decay of many different mRNAs and small noncoding RNAs. In general, RNases act as a global regulatory network extremely important for the regulation of RNA levels.
Topics: Bacteria; Endoribonucleases; Gene Expression; Gene Expression Regulation, Bacterial; Multienzyme Complexes; Polyribonucleotide Nucleotidyltransferase; RNA Helicases; RNA Processing, Post-Transcriptional; RNA Stability; RNA, Bacterial; Ribonucleases
PubMed: 20659169
DOI: 10.1111/j.1574-6976.2010.00242.x