regulatory rnas
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2022 ◽  
Vol 23 (2) ◽  
pp. 968
Author(s):  
Matthew W. Faber ◽  
Tommy V. Vo

As part of a complex network of genome control, long regulatory RNAs exert significant influences on chromatin dynamics. Understanding how this occurs could illuminate new avenues for disease treatment and lead to new hypotheses that would advance gene regulatory research. Recent studies using the model fission yeast Schizosaccharomyces pombe (S. pombe) and powerful parallel sequencing technologies have provided many insights in this area. This review will give an overview of key findings in S. pombe that relate long RNAs to multiple levels of chromatin regulation: histone modifications, gene neighborhood regulation in cis and higher-order chromosomal ordering. Moreover, we discuss parallels recently found in mammals to help bridge the knowledge gap between the study systems.


Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 428
Author(s):  
Aakash Koppula ◽  
Ahmed Abdelgawad ◽  
Jlenia Guarnerio ◽  
Mona Batish ◽  
Vijay Parashar

Circular RNAs (circRNAs) are regulatory RNAs which have recently been shown to have clinical significance in several diseases, including, but not limited to, various cancers, neurological diseases and cardiovascular diseases. The function of such regulatory RNAs is largely dependent on their subcellular localization. Several circRNAs have been shown to conduct antagonistic roles compared to the products of the linear isoforms, and thus need to be characterized distinctly from the linear RNAs. However, conventional fluorescent in situ hybridization (FISH) techniques cannot be employed directly to distinguish the signals from linear and circular isoforms because most circRNAs share the same sequence with the linear RNAs. In order to address this unmet need, we adapted the well-established method of single-molecule FISH by designing two sets of probes to differentiate the linear and circular RNA isoforms by virtue of signal colocalization. We call this method ‘circular fluorescent in situ hybridization’ (circFISH). Linear and circular RNAs were successfully visualized and quantified at a single-molecule resolution in fixed cells. RNase R treatment during the circFISH reduced the levels of linear RNAs while the circRNA levels remain unaltered. Furthermore, cells with shRNAs specific to circRNA showed the loss of circRNA levels, whereas the linear RNA levels were unaffected. The optimization of the in-situ RNase R treatment allowed the multiplexing of circFISH to combine it with organelle staining. CircFISH was found to be compatible with multiple sample types, including cultured cells and fresh-frozen and formalin-fixed tissue sections. Thus, we present circFISH as a versatile method for the simultaneous visualization and quantification of the distribution and localization of linear and circular RNA in fixed cells and tissue samples.


2022 ◽  
Vol 8 (1) ◽  
pp. 6
Author(s):  
Wei-Sheng Wu ◽  
Jordan S. Brown ◽  
Pin-Hao Chen ◽  
Sheng-Cian Shiue ◽  
Dong-En Lee ◽  
...  

Non-coding RNAs, such as miRNAs and piRNAs, play critical roles in gene regulation through base-pairing interactions with their target molecules. The recent development of the crosslinking, ligation, and sequencing of hybrids (CLASH) method has allowed scientists to map transcriptome-wide RNA–RNA interactions by identifying chimeric reads consisting of fragments from regulatory RNAs and their targets. However, analyzing CLASH data requires scientists to use advanced bioinformatics, and currently available tools are limited for users with little bioinformatic experience. In addition, many published CLASH studies do not show the full scope of RNA–RNA interactions that were captured, highlighting the importance of reanalyzing published data. Here, we present CLASH Analyst, a web server that can analyze raw CLASH data within a fully customizable and easy-to-use interface. CLASH Analyst accepts raw CLASH data as input and identifies the RNA chimeras containing the regulatory and target RNAs according to the user’s interest. Detailed annotation of the captured RNA–RNA interactions is then presented for the user to visualize within the server or download for further analysis. We demonstrate that CLASH Analyst can identify miRNA- and piRNA-targeting sites reported from published CLASH data and should be applicable to analyze other RNA–RNA interactions. CLASH Analyst is freely available for academic use.


2021 ◽  
Vol 1 (3) ◽  
pp. 403-423
Author(s):  
Elahe Soltani-Fard ◽  
Sina Taghvimi ◽  
Zahra Abedi Kichi ◽  
Christian Weber ◽  
Zahra Shabaninejad ◽  
...  

Non-coding RNAs (ncRNAs) are functional RNA molecules that comprise about 80% of both mammals and prokaryotes genomes. Recent studies have identified a large number of small regulatory RNAs in Escherichia coli and other bacteria. In prokaryotes, RNA regulators are a diverse group of molecules that modulate a wide range of physiological responses through a variety of mechanisms. Similar to eukaryotes, bacterial microRNAs are an important class of ncRNAs that play an important role in the development and secretion of proteins and in the regulation of gene expression. Similarly, riboswitches are cis-regulatory structured RNA elements capable of directly controlling the expression of downstream genes in response to small molecule ligands. As a result, riboswitches detect and respond to the availability of various metabolic changes within cells. The most extensive and most widely studied set of small RNA regulators act through base pairing with RNAs. These types of RNAs are vital for prokaryotic life, activating or suppressing important physiological processes by modifying transcription or translation. The majority of these small RNAs control responses to changes in environmental conditions. Finally, clustered regularly interspaced short palindromic repeat (CRISPR) RNAs, a newly discovered RNA regulator group, contains short regions of homology to bacteriophage and plasmid sequences that bacteria use to splice phage DNA as a defense mechanism. The detailed mechanism is still unknown but devoted to target homologous foreign DNAs. Here, we review the known mechanisms and roles of non-coding regulatory RNAs, with particular attention to riboswitches and their functions, briefly introducing translational applications of CRISPR RNAs in mammals.


Processes ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 2234
Author(s):  
Erika Nallely Orendain-Jaime ◽  
Nicolás Serafín-Higuera ◽  
Ana Gabriela Leija-Montoya ◽  
Gustavo Martínez-Coronilla ◽  
Misael Moreno-Trujillo ◽  
...  

Cancer is a deadly disease and, globally, represents the second leading cause of death in the world. Although it is a disease where several factors can help its development, virus induced infections have been associated with different types of neoplasms. However, in bacterial infections, their participation is not known for certain. Among the proposed approaches to oncogenesis risks in different infections are microRNAs (miRNAs). These are small molecules composed of RNA with a length of 22 nucleotides capable of regulating gene expression by directing protein complexes that suppress the untranslated region of mRNA. These miRNAs and other recently described, such as small RNAs (sRNAs), are deregulated in the development of cancer, becoming promising biomarkers. Thus, resulting in a study possibility, searching for new tools with diagnostic and therapeutic approaches to multiple oncological diseases, as miRNAs and sRNAs are main players of gene expression and host–infectious agent interaction. Moreover, sRNAs with limited complementarity are similar to eukaryotic miRNAs in their ability to modulate the activity and stability of multiple mRNAs. Here, we will describe the regulatory RNAs from viruses that have been associated with cancer and how sRNAs in bacteria can be related to this disease.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Stephan Klähn ◽  
Stefan Mikkat ◽  
Matthias Riediger ◽  
Jens Georg ◽  
Wolfgang R. Hess ◽  
...  

AbstractMicroorganisms evolved specific acclimation strategies to thrive in environments of high or fluctuating salinities. Here, salt acclimation in the model cyanobacterium Synechocystis sp. PCC 6803 was analyzed by integrating transcriptomic, proteomic and metabolomic data. A dynamic reorganization of the transcriptome occurred during the first hours after salt shock, e.g. involving the upregulation of genes to activate compatible solute biochemistry balancing osmotic pressure. The massive accumulation of glucosylglycerol then had a measurable impact on the overall carbon and nitrogen metabolism. In addition, we observed the coordinated induction of putative regulatory RNAs and of several proteins known for their involvement in other stress responses. Overall, salt-induced changes in the proteome and transcriptome showed good correlations, especially among the stably up-regulated proteins and their transcripts. We define an extended salt stimulon comprising proteins directly or indirectly related to compatible solute metabolism, ion and water movements, and a distinct set of regulatory RNAs involved in post-transcriptional regulation. Our comprehensive data set provides the basis for engineering cyanobacterial salt tolerance and to further understand its regulation.


2021 ◽  
Vol 8 ◽  
Author(s):  
Arundhati Das ◽  
Sharmishtha Shyamal ◽  
Tanvi Sinha ◽  
Smruti Sambhav Mishra ◽  
Amaresh C. Panda

Circular RNAs (circRNAs) are a newly discovered family of regulatory RNAs generated through backsplicing. Genome-wide profiling of circRNAs found that circRNAs are ubiquitously expressed and regulate gene expression by acting as a sponge for RNA-binding proteins (RBPs) and microRNAs (miRNAs). To identify circRNAs expressed in mouse skeletal muscle, we performed high-throughput RNA-sequencing of circRNA-enriched gastrocnemius muscle RNA samples, which identified more than 1,200 circRNAs. In addition, we have identified more than 14,000 and 15,000 circRNAs in aging human skeletal muscle tissue and satellite cells, respectively. A subset of abundant circRNAs was analyzed by RT-PCR, Sanger sequencing, and RNase R digestion assays to validate their expression in mouse skeletal muscle tissues. Analysis of the circRNA-miRNA-mRNA regulatory network revealed that conserved circNfix might associate with miR-204-5p, a suppressor of myocyte enhancer factor 2c (Mef2c) expression. To support the hypothesis that circNfix might regulate myogenesis by controlling Mef2c expression, silencing circNfix moderately reduced Mef2c mRNA expression and inhibited C2C12 differentiation. We propose that circNfix promotes MEF2C expression during muscle cell differentiation in part by acting as a sponge for miR-204-5p.


Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3212
Author(s):  
Feng Cheng ◽  
Jing Liang ◽  
Liyu Yang ◽  
Ganqiu Lan ◽  
Lixian Wang ◽  
...  

Intramuscular fat (IMF) content is a complex trait that affects meat quality and determines pork quality. In order to explore the potential mechanisms that affect the intramuscular fat content of pigs, a Large white × Min pigs F2 resource populations were constructed, then whole-transcriptome profile analysis was carried out for five low-IMF and five high-IMF F2 individuals. In total, 218 messenger RNA (mRNAs), 213 long non-coding RNAs (lncRNAs), 18 microRNAs (miRNAs), and 59 circular RNAs (circRNAs) were found to be differentially expressed in the longissimus dorsi muscle. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes annotations revealed that these differentially expressed (DE) genes or potential target genes (PTGs) of DE regulatory RNAs (lncRNAs, miRNAs, and circRNAs) are mainly involved in cell differentiation, fatty acid synthesis, system development, muscle fiber development, and regulating lipid metabolism. In total, 274 PTGs were found to be differentially expressed between low- and high-IMF pigs, which indicated that some DE regulatory RNAs may contribute to the deposition/metabolism of IMF by regulating their PTGs. In addition, we analyzed the quantitative trait loci (QTLs) of DE RNAs co-located in high- and low-IMF groups. A total of 97 DE regulatory RNAs could be found located in the QTLs related to IMF. Co-expression networks among different types of RNA and competing endogenous RNA (ceRNA) regulatory networks were also constructed, and some genes involved in type I diabetes mellitus were found to play an important role in the complex molecular process of intramuscular fat deposition. This study identified and analyzed some differential RNAs, regulatory RNAs, and PTGs related to IMF, and provided new insights into the study of IMF formation at the level of the genome-wide landscape.


2021 ◽  
Vol 11 ◽  
Author(s):  
Alberto Aranza-Martínez ◽  
Julio Sánchez-Pérez ◽  
Luis Brito-Elias ◽  
César López-Camarillo ◽  
David Cantú de León ◽  
...  

The resistance that Triple-Negative Breast Cancer (TNBC), the most aggressive breast cancer subtype, develops against radiotherapy is a complex phenomenon involving several regulators of cell metabolism and gene expression; understanding it is the only way to overcome it. We focused this review on the contribution of the two leading classes of regulatory non-coding RNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), against ionizing radiation-based therapies. We found that these regulatory RNAs are mainly associated with DNA damage response, cell death, and cell cycle regulation, although they regulate other processes like cell signaling and metabolism. Several regulatory RNAs regulate multiple pathways simultaneously, such as miR-139-5p, the miR-15 family, and the lncRNA HOTAIR. On the other hand, proteins such as CHK1 and WEE1 are targeted by several regulatory RNAs simultaneously. Interestingly, the study of miRNA/lncRNA/mRNA regulation axes increases, opening new avenues for understanding radioresistance. Many of the miRNAs and lncRNAs that we reviewed here can be used as molecular markers or targeted by upcoming therapeutic options, undoubtedly contributing to a better prognosis for TNBC patients.


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