MicroRNA-mediated gene silencing: are we close to a unifying model?

2012 ◽  
Vol 3 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Victoria James ◽  
Sybil C.K. Wong ◽  
Tyson V. Sharp
Keyword(s):  
Gene Expression ◽  
Gene Silencing ◽  
Messenger Rna ◽  
Transcriptional Regulators ◽  
Effector Proteins ◽  
Specific Reference ◽  
Functional Studies ◽  
Non Coding Rna ◽  
Almost All ◽  
Terminal Effector

AbstractMicroRNAs (miRNAs) comprise a group of small non-coding RNA –21 nucleotides in length. They act as post-transcriptional regulators of gene expression by forming base pairing interactions with target messenger RNA (mRNA). At least 1000 miRNAs are predicted to be expressed in humans and are encoded for in the genome of almost all organisms. Functional studies indicate that every cellular process studied thus far is regulated at some level by miRNAs. Given this expansive role, it is not surprising that disruption of this crucial pathway underlies the initiation of, or in the least, contributes to the development and progression of numerous human diseases and physiological disorders. This review will focus on the latest developments in uncovering the mechanism(s) of miRNA-mediated silencing with specific reference to the function of terminal effector proteins, how translation of target mRNA is inhibited and whether we are moving towards understanding this fundamental gene silencing paradigm.

scholarly journals Xist-seeded nucleation sites form local concentration gradients of silencing proteins to inactivate the X-chromosome

2020 ◽  
Author(s):  
Yolanda Markaki ◽  
Johnny Gan Chong ◽  
Christy Luong ◽  
Shawn Y.X. Tan ◽  
Yuying Wang ◽  
...  
Keyword(s):  
Gene Silencing ◽  
X Chromosome ◽  
Effector Proteins ◽  
Local Concentration ◽  
Concentration Gradients ◽  
Rna Molecules ◽  
Intrinsically Disordered ◽  
Chromatin Interactions ◽  
Non Coding Rna ◽  
Xist Rna

AbstractThe long non-coding RNA Xist exploits numerous effector proteins to progressively induce gene silencing across the X chromosome and form the inactive X (Xi)-compartment. The mechanism underlying formation of the chromosome-wide Xi-compartment is poorly understood. Here, we find that formation of the Xi-compartment is induced by ∼50 locally confined granules, where two Xist RNA molecules nucleate supra-molecular complexes (SMCs) of interacting proteins. Xist-SMCs are transient structures that concentrate rapidly recycling proteins in the X by increasing protein binding affinity. We find that gene silencing originates at Xist-SMCs and propagates across the entire chromosome over time, achieved by Polycomb-mediated coalescence of chromatin regions and aggregation, via its intrinsically disordered domains, of the critical silencing factor SPEN. Our results suggest a new model for X chromosome inactivation, in which Xist RNA induces macromolecular crowding of heterochromatinizing proteins near distinct sites which ultimately increases their density throughout the chromosome. This mechanism enables deterministic gene silencing without the need for Xist ribonucleoprotein complex-chromatin interactions at each target gene.

scholarly journals MicroRNAs: From Junk RNA to Life Regulators and Their Role in Cardiovascular Disease

2021 ◽  
Vol 11 (4) ◽  
pp. 230-254
Author(s):  
Federica Amodio ◽  
Martina Caiazza ◽  
Fabio Fimiani ◽  
Paolo Calabrò ◽  
Giuseppe Limongelli
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Cell Communication ◽  
Transcriptional Level ◽  
Negative Regulators ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
New Perspective ◽  
Therapeutic Tools ◽  
The Stability

MicroRNAs (miRNAs) are single-stranded small non-coding RNA (18–25 nucleotides) that until a few years ago were considered junk RNA. In the last twenty years, they have acquired more importance thanks to the understanding of their influence on gene expression and their role as negative regulators at post-transcriptional level, influencing the stability of messenger RNA (mRNA). Approximately 5% of the genome encodes miRNAs which are responsible for regulating numerous signaling pathways, cellular processes and cell-to-cell communication. In the cardiovascular system, miRNAs control the functions of various cells, such as cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts, playing a role in physiological and pathological processes and seeming also related to variations in contractility and hereditary cardiomyopathies. They provide a new perspective on the pathophysiology of disorders such as hypertrophy, fibrosis, arrhythmia, inflammation and atherosclerosis. MiRNAs are differentially expressed in diseased tissue and can be released into the circulation and then detected. MiRNAs have become interesting for the development of new diagnostic and therapeutic tools for various diseases, including heart disease. In this review, the concept of miRNAs and their role in cardiomyopathies will be introduced, focusing on their potential as therapeutic and diagnostic targets (as biomarkers).

scholarly journals Assessing the Functionality of RNA Interference (RNAi) in the Phloem-feeding Maize pest Dalbulus maidis

2021 ◽  
Author(s):  
Tara-Kay L. Jones ◽  
Julio S. Bernal ◽  
Raul F. Medina
Keyword(s):  
Gene Expression ◽  
Rna Interference ◽  
Gene Silencing ◽  
Pest Control ◽  
Messenger Rna ◽  
Specific Gene ◽  
Insect Vector ◽  
Dalbulus Maidis ◽  
Spiroplasma Kunkelii ◽  
Phloem Feeding

Dalbulus maidis [(DeLong & Wolcott), corn leafhopper], a phloem-feeding insect, is the most efficient vector of maize stunting pathogens (Spiroplasma kunkelii, Maize bushy stunt phytoplasma, and Maize rayado fino virus) in the Americas. Studies involving gene editing in insects are rapidly providing information that can potentially be used for insect vector and plant disease control. RNA interference (RNAi), a sequence-specific gene silencing method, is one of the most widely used molecular tools in functional genomics studies. RNAi uses exogenous double-stranded RNA (dsRNA) or small interfering RNA (siRNA) to prevent the production of proteins by inhibiting the expression of their corresponding messenger RNA (mRNA). In this study, we measured the efficacy of gene silencing, and its effects on D. maidis mortality as proof of concept that RNAi is a viable tool for use in genetic pest control of phloem-feeding insects. Oral delivery of dsRNA using an artificial diet was used to silence two key insect genes, vacuolar ATP synthase subunit B, and subunit D (V-ATPase B and V-ATPase D). Our results showed reduced gene expression of V-ATPase B and V-ATPase D after ingestion of dsRNA, and significantly higher mortality, and wing deformation, associated with reduced gene expression, compared to control insects that were not orally fed dsRNA. These results reveal RNAi as a viable tool for use in genetic pest control of phloem-feeding insects, and a way for further functional genomic studies, such as identification of potential target genes for either population suppression or population replacement of this vector of maize diseases.

scholarly journals CSDE1 controls gene expression through the miRNA-mediated decay machinery

2020 ◽  
Vol 3 (4) ◽  
pp. e201900632
Author(s):  
Pavan Kumar Kakumani ◽  
Louis-Mathieu Harvey ◽  
François Houle ◽  
Tanit Guitart ◽  
Fátima Gebauer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Silencing ◽  
Rna Binding ◽  
Control Of Gene Expression ◽  
Rna Molecules ◽  
Stem Cell Maintenance ◽  
Argonaute Proteins ◽  
Posttranscriptional Gene Regulation ◽  
Non Coding Rna ◽  
Mirna Pathway

In animals, miRNAs are the most prevalent small non-coding RNA molecules controlling posttranscriptional gene regulation. The Argonaute proteins (AGO) mediate miRNA-guided gene silencing by recruiting multiple factors involved in translational repression, deadenylation, and decapping. Here, we report that CSDE1, an RNA-binding protein linked to stem cell maintenance and metastasis in cancer, interacts with AGO2 within miRNA-induced silencing complex and mediates gene silencing through its N-terminal domains. We show that CSDE1 interacts with LSM14A, a constituent of P-body assembly and further associates to the DCP1–DCP2 decapping complex, suggesting that CSDE1 could promote the decay of miRNA-induced silencing complex-targeted mRNAs. Together, our findings uncover a hitherto unknown mechanism used by CSDE1 in the control of gene expression mediated by the miRNA pathway.

scholarly journals Long Non-Coding RNAs and Their Potential Roles in the Vector–Host–Pathogen Triad

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 56
Author(s):  
Parwez Ahmad ◽  
Chaima Bensaoud ◽  
Imen Mekki ◽  
Mujeeb Ur Rehman ◽  
Michail Kotsyfakis
Keyword(s):  
Gene Expression ◽  
Species Interactions ◽  
Messenger Rna ◽  
Defense Mechanisms ◽  
Developmental Stages ◽  
Regulation Of Gene Expression ◽  
Host Pathogen Interactions ◽  
Non Coding Rna ◽  
Host Pathogen ◽  
Time Specific

Long non-coding (lnc)RNAs have emerged as critical regulators of gene expression and are involved in almost every cellular process. They can bind to other molecules including DNA, proteins, or even other RNA types such messenger RNA or small RNAs. LncRNAs are typically expressed at much lower levels than mRNA, and their expression is often restricted to tissue- or time-specific developmental stages. They are also involved in several inter-species interactions, including vector–host–pathogen interactions, where they can be either vector/host-derived or encoded by pathogens. In these interactions, they function via multiple mechanisms including regulating pathogen growth and replication or via cell-autonomous antimicrobial defense mechanisms. Recent advances suggest that characterizing lncRNAs and their targets in different species may hold the key to understanding the role of this class of non-coding RNA in interspecies crosstalk. In this review, we present a general overview of recent studies related to lncRNA-related regulation of gene expression as well as their possible involvement in regulating vector–host–pathogen interactions.

scholarly journals Mitochondrial Glucocorticoid Receptors and Their Actions

2021 ◽  
Vol 22 (11) ◽  
pp. 6054
Author(s):  
Ioanna Kokkinopoulou ◽  
Paraskevi Moutsatsou
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptors ◽  
Mitochondrial Gene ◽  
Cell Types ◽  
Ros Generation ◽  
Mitochondrial Gene Expression ◽  
Mitochondrial Energy Metabolism ◽  
Bcl2 Family ◽  
Cellular Processes ◽  
Almost All

Mitochondria are membrane organelles present in almost all eukaryotic cells. In addition to their well-known role in energy production, mitochondria regulate central cellular processes, including calcium homeostasis, Reactive Oxygen Species (ROS) generation, cell death, thermogenesis, and biosynthesis of lipids, nucleic acids, and steroid hormones. Glucocorticoids (GCs) regulate the mitochondrially encoded oxidative phosphorylation gene expression and mitochondrial energy metabolism. The identification of Glucocorticoid Response Elements (GREs) in mitochondrial sequences and the detection of Glucocorticoid Receptor (GR) in mitochondria of different cell types gave support to hypothesis that mitochondrial GR directly regulates mitochondrial gene expression. Numerous studies have revealed changes in mitochondrial gene expression alongside with GR import/export in mitochondria, confirming the direct effects of GCs on mitochondrial genome. Further evidence has made clear that mitochondrial GR is involved in mitochondrial function and apoptosis-mediated processes, through interacting or altering the distribution of Bcl2 family members. Even though its exact translocation mechanisms remain unknown, data have shown that GR chaperones (Hsp70/90, Bag-1, FKBP51), the anti-apoptotic protein Bcl-2, the HDAC6- mediated deacetylation and the outer mitochondrial translocation complexes (Tom complexes) co-ordinate GR mitochondrial trafficking. A role of mitochondrial GR in stress and depression as well as in lung and hepatic inflammation has also been demonstrated.

scholarly journals Hops (Humulus lupulus L.) as a Novel Multipurpose Crop for the Mediterranean Region of Europe: Challenges and Opportunities of Their Cultivation

Agriculture ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 484
Author(s):  
Francesco Rossini ◽  
Giuseppe Virga ◽  
Paolo Loreti ◽  
Nicolò Iacuzzi ◽  
Roberto Ruggeri ◽  
...  
Keyword(s):  
Humulus Lupulus ◽  
Specific Reference ◽  
Research Activity ◽  
Plant Parts ◽  
Craft Beer ◽  
Recent Success ◽  
Natural Medicine ◽  
Humulus Lupulus L ◽  
Challenges And Opportunities ◽  
Almost All

The common hop (Humulus lupulus L.) is a dioecious perennial climbing plant, mainly known for the use of its female inflorescences (cones or, simply, “hops”) in the brewing industry. However, the very first interest towards hops was due to its medicinal properties. Actually, the variety of compounds present in almost all plant parts were (and still are) used to treat or prevent several ailments and metabolic disorders, from insomnia to menopausal symptoms as well as obesity and even cancer. Although hops are predominantly grown for hopping beer, the increasing interest in natural medicine is widening new interesting perspectives for this crop. Moreover, the recent success of the craft beer sector all over the world, made the cultivated hop come out from its traditional growing areas. Particularly, in Europe this resulted in a movement towards southern countries such as Italy, which added itself to the already existing hop industry in Portugal and Spain. In these relatively new environments, a complete knowledge and expertise of hop growing practices is lacking. Overall, while many studies were conducted globally on phytochemistry, bioactivity, and the genetics of hops, results from public research activity on basic hop agronomy are very few and discontinuous as well. The objective of this article is to provide an overview of possible uses, phenology, and agronomic aspects of hops, with specific reference to the difficulties and opportunities this crop is experiencing in the new growing areas, under both conventional and organic farming. The present review aims to fill a void still existing for this topic in the literature and to give directions for farmers that want to face the cultivation of such a challenging crop.

scholarly journals Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 350
Author(s):  
Julianty Frost ◽  
Mark Frost ◽  
Michael Batie ◽  
Hao Jiang ◽  
Sonia Rocha
Keyword(s):  
Gene Expression ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Regulator ◽  
Hydroxylase Activity ◽  
Control Of Gene Expression ◽  
Prolyl Hydroxylases ◽  
Chromatin Organisation ◽  
Sense And Respond ◽  
Almost All ◽  
And Function

Hypoxia—reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OGDs in the control of gene expression in response to hypoxia and their relevance to human biology and health.

scholarly journals Phylogenetic comparison and splice site conservation of eukaryotic U1 snRNP-specific U1-70K gene family

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tao Fan ◽  
Yu-Zhen Zhao ◽  
Jing-Fang Yang ◽  
Qin-Lai Liu ◽  
Yuan Tian ◽  
...  
Keyword(s):  
Gene Family ◽  
Splice Site ◽  
Messenger Rna ◽  
Expression Patterns ◽  
Protein Structures ◽  
Single Copy ◽  
Central Component ◽  
Animal Kingdom ◽  
Functional Studies ◽  
U1 Snrnp

AbstractEukaryotic cells can expand their coding ability by using their splicing machinery, spliceosome, to process precursor mRNA (pre-mRNA) into mature messenger RNA. The mega-macromolecular spliceosome contains multiple subcomplexes, referred to as small nuclear ribonucleoproteins (snRNPs). Among these, U1 snRNP and its central component, U1-70K, are crucial for splice site recognition during early spliceosome assembly. The human U1-70K has been linked to several types of human autoimmune and neurodegenerative diseases. However, its phylogenetic relationship has been seldom reported. To this end, we carried out a systemic analysis of 95 animal U1-70K genes and compare these proteins to their yeast and plant counterparts. Analysis of their gene and protein structures, expression patterns and splicing conservation suggest that animal U1-70Ks are conserved in their molecular function, and may play essential role in cancers and juvenile development. In particular, animal U1-70Ks display unique characteristics of single copy number and a splicing isoform with truncated C-terminal, suggesting the specific role of these U1-70Ks in animal kingdom. In summary, our results provide phylogenetic overview of U1-70K gene family in vertebrates. In silico analyses conducted in this work will act as a reference for future functional studies of this crucial U1 splicing factor in animal kingdom.

Sign in / Sign up

Export Citation Format

Share Document