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 Compendium of Methods to Uncover RNA-Protein Interactions In Vivo

2021 ◽  
Vol 4 (1) ◽  
pp. 22
Author(s):  
Mrinmoyee Majumder ◽  
Viswanathan Palanisamy
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Expression Patterns ◽  
Control Of Gene Expression ◽  
Regulatory Pathways ◽  
Advantages And Disadvantages ◽  
Protein Nucleic Acid

Control of gene expression is critical in shaping the pro-and eukaryotic organisms’ genotype and phenotype. The gene expression regulatory pathways solely rely on protein–protein and protein–nucleic acid interactions, which determine the fate of the nucleic acids. RNA–protein interactions play a significant role in co- and post-transcriptional regulation to control gene expression. RNA-binding proteins (RBPs) are a diverse group of macromolecules that bind to RNA and play an essential role in RNA biology by regulating pre-mRNA processing, maturation, nuclear transport, stability, and translation. Hence, the studies aimed at investigating RNA–protein interactions are essential to advance our knowledge in gene expression patterns associated with health and disease. Here we discuss the long-established and current technologies that are widely used to study RNA–protein interactions in vivo. We also present the advantages and disadvantages of each method discussed in the review.

scholarly journals miRNAome expression profiles in the gonads of adultMelopsittacus undulatus

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4615 ◽  
Author(s):  
Lan Jiang ◽  
Qingqing Wang ◽  
Jue Yu ◽  
Vinita Gowda ◽  
Gabriel Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Early Development ◽  
Expression Profiles ◽  
Critical Role ◽  
Genomic Research ◽  
Go Annotation ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Mirnas Expression ◽  
Paired End Sequencing

The budgerigar (Melopsittacus undulatus) is one of the most widely studied parrot species, serving as an excellent animal model for behavior and neuroscience research. Until recently, it was unknown how sexual differences in the behavior, physiology, and development of organisms are regulated by differential gene expression. MicroRNAs (miRNAs) are endogenous short non-coding RNA molecules that can post-transcriptionally regulate gene expression and play a critical role in gonadal differentiation as well as early development of animals. However, very little is known about the role gonadal miRNAs play in the early development of birds. Research on the sex-biased expression of miRNAs in avian gonads are limited, and little is known aboutM. undulatus. In the current study, we sequenced two small non-coding RNA libraries made from the gonads of adult male and female budgerigars using Illumina paired-end sequencing technology. We obtained 254 known and 141 novel miRNAs, and randomly validated five miRNAs. Of these, three miRNAs were differentially expressed miRNAs and 18 miRNAs involved in sexual differentiation as determined by functional analysis with GO annotation and KEGG pathway analysis. In conclusion, this work is the first report of sex-biased miRNAs expression in the budgerigar, and provides additional sequences to the avian miRNAome database which will foster further functional genomic research.

scholarly journals Visualizing the translation and packaging of HIV-1 full-length RNA

2020 ◽  
Vol 117 (11) ◽  
pp. 6145-6155 ◽  
Author(s):  
Jianbo Chen ◽  
Yang Liu ◽  
Bin Wu ◽  
Olga A. Nikolaitchik ◽  
Preeti R. Mohan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Molecule ◽  
Rna Binding ◽  
Virus Assembly ◽  
Full Length ◽  
Rna Molecules ◽  
Rna Translation ◽  
Translation Template ◽  
A Genome ◽  
Hiv 1

HIV-1 full-length RNA (HIV-1 RNA) plays a central role in viral replication, serving as a template for Gag/Gag-Pol translation and as a genome for the progeny virion. To gain a better understanding of the regulatory mechanisms of HIV-1 replication, we adapted a recently described system to visualize and track translation from individual HIV-1 RNA molecules in living cells. We found that, on average, half of the cytoplasmic HIV-1 RNAs are being actively translated at a given time. Furthermore, translating and nontranslating RNAs are well mixed in the cytoplasm; thus, Gag biogenesis occurs throughout the cytoplasm without being constrained to particular subcellular locations. Gag is an RNA binding protein that selects and packages HIV-1 RNA during virus assembly. A long-standing question in HIV-1 gene expression is whether Gag modulates HIV-1 RNA translation. We observed that despite its RNA-binding ability, Gag expression does not alter the proportion of translating HIV-1 RNA. Using single-molecule tracking, we found that both translating and nontranslating RNAs exhibit dynamic cytoplasmic movement and can reach the plasma membrane, the major HIV-1 assembly site. However, Gag selectively packages nontranslating RNA into the assembly complex. These studies illustrate that although HIV-1 RNA serves two functions, as a translation template and as a viral genome, individual RNA molecules carry out only one function at a time. These studies shed light on previously unknown aspects of HIV-1 gene expression and regulation.

scholarly journals Molecular Mechanisms, Diagnostic Aspects and Therapeutic Opportunities of Micro Ribonucleic Acids in Atrial Fibrillation

2020 ◽  
Vol 21 (8) ◽  
pp. 2742 ◽  
Author(s):  
Allan Böhm ◽  
Marianna Vachalcova ◽  
Peter Snopek ◽  
Ljuba Bacharova ◽  
Dominika Komarova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atrial Fibrillation ◽  
Molecular Mechanisms ◽  
Wide Spectrum ◽  
Regulation Of Gene Expression ◽  
Review Article ◽  
Ribonucleic Acids ◽  
Rna Molecules ◽  
Diagnostic Aspects ◽  
Non Coding Rna

Micro ribonucleic acids (miRNAs) are short non-coding RNA molecules responsible for regulation of gene expression. They are involved in many pathophysiological processes of a wide spectrum of diseases. Recent studies showed their involvement in atrial fibrillation. They seem to become potential screening biomarkers for atrial fibrillation and even treatment targets for this arrhythmia. The aim of this review article was to summarize the latest knowledge about miRNA and their molecular relation to the pathophysiology, diagnosis and treatment of atrial fibrillation.

238 RNA BINDING PROTEIN EXPRESSION IN CULTURED EARLY BOVINE EMBRYOS

2010 ◽  
Vol 22 (1) ◽  
pp. 277
Author(s):  
L. A. Favetta ◽  
E. Van de Laar ◽  
W. A. King ◽  
J. LaMarre
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Bovine Embryo ◽  
Rt Pcr ◽  
Control Of Gene Expression ◽  
Morula Stage ◽  
Bovine Oocytes

The control of gene expression in the early embryo requires a highly regulated turnover of specific mRNA, particularly those of maternal origin, as the embryo becomes transcriptionally autonomous. In cattle, the period during which maternal transcripts persist can last 72 to 96 h or longer, suggesting a dynamic, regulated interplay between factors that protect transcripts before this point and those that subsequently facilitate decay. Some decay pathways for specific embryonic transcripts are now known, but many are not. In somatic cells, mRNA decay is often mediated by interactions between defined sequence elements (ARE) in the 3′ untranslated region of important target genes and specific RNA-binding proteins (AUBP) that promote or inhibit decay of the associated transcript. These have not been extensively characterized in embryos. We hypothesized that changes in the pattern of expression of one or several AUBP in the developing bovine embryo would support a role for these proteins in mRNA turnover and the control of gene expression. We, therefore, evaluated the expression of different AUBP (HuR, AUF1, TTP) in bovine oocytes and early embryos in vitro. Bovine oocytes obtained at slaughter were matured, fertilized, and cultured using standard protocols. Oocytes and embryos from different stages were either placed in Trizol for subsequent RNA isolation and RT-PCR analysis or fixed in 4% paraformaldehyde and subsequently processed for immunohistochemical detection of AUBP. Analysis by RT-PCR revealed that AUF1, an mRNA destabilizing protein, was expressed at all stages examined (immature oocyte, mature oocyte, 2 to 4 cells, 8 to 16 cells, morulae, and blastocyst) except in morulae. Another mRNA destabilizing protein, TTP, was expressed at the morula stage only. An mRNA stabilizing factor, HuR, was expressed at all stages except the morula. Immunohistochemical analysis revealed that the pattern of protein expression for AUF1 and TTP essentially mirrored that observed at the RNA level as detected by RT-PCR. Together, these results show that AUBP expression in the early bovine embryo is dynamic, with RNA-binding proteins present at all times during development and changes in expression evident at the morula stage. This suggests that modification of presynthesized (i.e. maternal) AUBP is likely to control mRNA decay during the maternal to embryonic transition (8-cell stage) and that the expression of TTP at the morula stage might mark the onset of embryonic control of mRNA stability. Research was supported by NSERC, OMAFRA, and the Canada Research Chairs Program.

scholarly journals Cip1 and Cip2 Are Novel RNA-Recognition-Motif Proteins That Counteract Csx1 Function during Oxidative Stress

2006 ◽  
Vol 17 (3) ◽  
pp. 1176-1183 ◽  
Author(s):  
Victoria Martín ◽  
Miguel A. Rodríguez-Gabriel ◽  
W. Hayes McDonald ◽  
Stephen Watt ◽  
John R. Yates ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Stress Response ◽  
Protein Identification ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Bzip Transcription Factor ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Control Of Gene Expression

Eukaryotic cells reprogram their global patterns of gene expression in response to stress. Recent studies in Schizosaccharomyces pombe showed that the RNA-binding protein Csx1 plays a central role in controlling gene expression during oxidative stress. It does so by stabilizing atf1+ mRNA, which encodes a subunit of a bZIP transcription factor required for gene expression during oxidative stress. Here, we describe two related proteins, Cip1 and Cip2, that were identified by multidimensional protein identification technology (MudPIT) as proteins that coprecipitate with Csx1. Cip1 and Cip2 are cytoplasmic proteins that have RNA recognition motifs (RRMs). Neither protein is essential for viability, but a cip1Δ cip2Δ strain grows poorly and has altered cellular morphology. Genetic epistasis studies and whole genome expression profiling show that Cip1 and Cip2 exert posttranscriptional control of gene expression in a manner that is counteracted by Csx1. Notably, the sensitivity of csx1Δ cells to oxidative stress and their inability to induce expression of Atf1-dependent genes are partially rescued by cip1Δ and cip2Δ mutations. This study emphasizes the importance of a modulated mRNA stability in the eukaryotic stress response pathways and adds new information to the role of RNA-binding proteins in the oxidative stress response.

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.

MicroRNA profiling in cancer

2011 ◽  
Vol 121 (4) ◽  
pp. 141-158 ◽  
Author(s):  
Reinhold Munker ◽  
George A. Calin
Keyword(s):  
Gene Expression ◽  
Expression Profiling ◽  
Cell Biology ◽  
Human Cancer ◽  
Rare Tumour ◽  
Rna Molecules ◽  
Future Developments ◽  
Microrna Profiling ◽  
Non Coding Rna ◽  
Diagnosis Of Cancer

The diagnosis of cancer has undergone major changes in the last 40 years. Once based purely on morphology, diagnosis has come to incorporate immunological, cytogenetic and molecular methods. Many cancers, especially leukaemias, are now defined by molecular markers. Gene expression profiling based on mRNA has led to further refinement of the classification and diagnosis of cancer. More recently, miRNAs (microRNAs), among other small non-coding RNA molecules, have been discovered and found to be major players in cell biology. miRNAs, having both oncogenic and tumour-suppressive functions, are dysregulated in many types of cancer. miRNAs also interfere with metastasis, apoptosis and invasiveness of cancer cells. In the present review, we discuss recent advances in miRNA profiling in human cancer. We discuss both frequent and rare tumour types and give an outlook on future developments.

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