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Epigenetics in Sperm, Epigenetic Diagnostics, and Transgenerational Inheritance
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Jennifer L. M. Thorson, Millissia Ben Maamar, Michael K. Skinner
Non-coding RNA molecules can act as epigenetic factors (37) (Figure 7.1). These are small RNA molecules that do not code for a protein, but rather function as RNA to regulate gene expression. The non-coding RNA molecules that act as epigenetic factors have secondary structure to facilitate DNA and protein interactions, but are not DNA sequence-dependent, so the majority do not depend on having a nucleotide sequence that is complimentary to a specific DNA or RNA region in order to function. Long non-coding RNAs (lncRNAs) (38) and small non-coding RNAs (sncRNAs) are the two major types. The sncRNA have many sub-families such as transfer RNA-derived small RNAs (tsRNAs) (39), which are examples of ncRNA classes that are present in sperm and can act as epigenetic factors that affect subsequent generations (39,40).
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Two main technologies have been pursued to develop RNA-based therapeutics, antisense and RNA interference (RNAi), and these are described in detail below. Both antisense and RNAi therapeutics have taken many decades to develop, partly due to the fragility of RNA toward premature degradation. For this reason, many different types of backbone modified nucleic acid structures have been developed, and these are described below in a separate section, although they can be used for either of the main therapeutic strategies. Also, within the area of RNAi therapeutics, two types of small RNA molecules, small interfering RNAs (siRNAs) and microRNAs (miRNAs), have been developed and are described below. Finally, there has been significant amount of research into ribozymes, engineered RNA fragments with enzymic activity, and small molecules that can bind and target RNA. Although of academic interest and described below, neither of these technologies have reached late-stage clinical trials.
Markers of Sensitivity and Resistance to EGFR Inhibitors in Colorectal Cancer
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Jose G. Monzon, Janet E. Dancey
A unique mechanism of KRAS activation has recently been hypothesized that may predict for response to anti-EGFR moAbs. MicroRNAs (miRNAs) are a class of small RNAs that play a role in gene regulation in the cell. Binding of miRNA to messenger RNA (mRNA) recruits and activates an RNA-induced silencing complex to the target message [98].
LncRNA NEAT1 regulate diffuse large B-cell lymphoma by targeting miR-495-3p/PD-L1 axis
Published in Immunopharmacology and Immunotoxicology, 2022
Jun Yuan, Jie Yang, Ruicang Wang, Hongling Hao, Jie Li
Long noncoding RNAs (lncRNAs) are a class of small RNA transcripted by RNA polymerase II [18], which are usually longer than 200 nucleotides and do not have a readable frame [19]. lncRNAs can regulate gene expression at epigenetic, transcriptional and post-transcriptional levels by interacting with DNA, RNA and proteins [20]. LncRNAs are reported to be abnormally expressed in a variety of tumors [21,22]. In DLBCL, HULC [23], LUNAR1 [24] and MALAT-1 [25] expression were higher than that in normal tissues and cells, indicating that lncRNA plays a significant role in DLBCL. Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) is a crucial structural constituent of paraspeckles, which has been reported to be associated with colorectal cancer [26], melanoma [27], multiple myeloma [28]. However, the roles of NEAT1 in DLBCL have not been fully elucidated. This study aims to explore the function and regulation of NEAT1 in DLBCL.
Do small RNAs have potential in disease diagnosis and treatment?
Published in Expert Review of Molecular Diagnostics, 2021
Sushila Maan, Kanisht Batra, Narender Singh Maan
Several classes of small RNAs have emerged recently. Numerous aspects of their origins, structures, related effector proteins, and biological roles have led to the identification of three main categories: short interfering (si)RNAs, micro (mi)RNAs, and piwi-interacting (pi)RNAs. These small RNAs are regulated by two recently discovered miRNA-regulatory RNAs, namely competing endogenous (ce)RNA and circular (circ)RNA. Recently, another class of small RNAs (17–18 nt in length) was discovered in animals using deep sequencing approaches and these are found to be associated with transcription initiation (‘tiRNAs’) and splice sites (‘spliRNAs’). Initial studies suggest that they may play a role in nucleosome positioning and/or be involved in chromatin organization. There are also other reports of less distinct classes of promoter-associated RNAs called PASRs, TSSa-RNAs, and PROMPTS, some of which may play a role in RNA-directed transcriptional gene silencing.
Extracellular vesicles and chronic inflammation during HIV infection
Published in Journal of Extracellular Vesicles, 2019
Paula Soledad Pérez, María Albertina Romaniuk, Gabriel A. Duette, Zezhou Zhao, Yiyao Huang, Lorena Martin-Jaular, Kenneth W Witwer, Clotilde Théry, Matías Ostrowski
The miRNA and small RNA findings reviewed here raise the possibility of developing small RNA drugs to inhibit or enhance identified small RNAs. However, some of the findings are also puzzling and require additional investigations. For example, in the case of the signalling studies, it is difficult to understand how small RNAs carried inside an EV would engage a toll-like receptor, since the small RNA and the receptor are separated by the EV membrane bilayer. Thus, the EV-associated small RNA should be somehow transported across the membrane, or instead, the miRNA and receptor should remain functional as the EV is degraded by endosome acidification. Alternatively, the effects attributed to EV RNA could actually be due to extra-EV RNA, perhaps enhanced by association with the surface of the EV.