China
Africa
Explore chapters and articles related to this topic
Epigenetic and Assisted Reproduction Experimental Studies
Published in Cristina Camprubí, Joan Blanco, Epigenetics and Assisted Reproduction, 2018
Celia Corral-Vazquez, Ester Anton
As well as gene silencing, retrotransposon control in germ cells is an essential issue for spermatogenesis development. For this reason, piRNAs are considered an important piece in a correct sperm differentiation process. It has been observed in male mice that the interruption of piRNA biosynthesis causes infertility, with non-functional sperm cells. Generally, piRNAs are classified as prepachytene and pachytene piRNAs, depending on the spermatogenesis stage in which they are synthesized (35). Expression of prepachytene piRNAs has been detected in spermatogonia since fetal stages. These piRNAs can be generated either by the primary or the secondary “ping-pong” mechanisms (32). They are associated with either MIWI2 or MILI proteins (36). It has been observed that the absence of these proteins causes the activation and hypomethylation of transposable elements, such as IAP (Intracisternal A-partile) and LINE1. For this reason, it has been suggested that these PIWI proteins contribute to suppress transposon transcription either by promoting the methylation of their DNA loci, or by eliminating them post-transcriptionally through piRNA action. Additionally, MIWI2 is directly involved in piRNA synthesis from antisense transposable sequences, acting as a counter mechanism for deleting these active retrotransposons (35). Regarding pachytene piRNAs biosynthesis, it can only occur by the primary mechanism (32). These piRNAs are attached to MILI or MIWI, which can only act at a post-transcriptional level by silencing transposable elements, without altering methylation patterns (35).
The Indispensable Soma Hypothesis in Aging
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
piRNAs are defined by their specific binding to the PIWI (P-element Induced WImpy testis) subfamily of the Argonaute/PIWI family proteins [106]. One of the fidelity preservation mechanisms deployed by the germline involves the piRNA and retrotransposon defense mechanisms [107,108]. piRNA silencing may have an impact (through very intricate mechanisms) on the maintenance of the stability of the germ cell genome [109]. In somatic cells, PIWI may act in association with the conserved flamenco piRNA cluster and prevent retroviral elements from propagating and from damaging germ cells [110].
Lipid Nanocarriers for Oligonucleotide Delivery to the Brain
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Andreia F. Jorge, Santiago Grijalvo, Alberto Pais, Ramón Eritja
The RNAi pathway was firstly identified by Mello and Fire [40], and it is a natural regulatory process whereby small-sized double-stranded RNAs (dsRNAs) downregulate gene expression. These endogenous ncRNAs are active regulators of gene expression acting at a posttranscriptional level and are commonly classified into three main subclasses in animals: (i) small interfering RNA (siRNA), (ii) microRNA (miRNA) and (iii) Piwi-interacting RNA (piRNA). Endogenously, siRNA are diced from longer RNA transcripts by an enzyme known as Dicer [41] to generate an ODN 21–23 nt in length, while miRNAs are processed from longer hairpin transcripts by the consecutive action of two RNase III proteins, Drosha and Dicer [42], to end up with a ~22 nt length. After breakdown, siRNA and miRNA are loaded into the RNA-induced silencing complex (RISC) in a double-stranded conformation. This complex is composed by Dicer, Argonaute2 (Ago2) and transactivation response RNA-binding (TRBP) proteins [43, 44]. In the case of siRNA, a process deemed RISC maturation triggers the release of the sense strand, whereas the antisense strand is paired to a complementary mRNA. The perfect match between antisense siRNA and mRNA results in an endonucleolytic cleavage of the target mRNA promoted by the slicing effector Ago2 of the RNAi process [45]. Conversely, complementary between the seed region of one strand of the hairpin duplex of miRNA (positions 2–8 from the 5’ miRNA) with the 3’ untranslated region (3’ UTR) of the target mRNA is the only prerequisite to silence the expression of the target genes through mechanisms of translation repression and mRNA destabilisation [46]. Fully complementarity between miRNA and mRNA activates a process of degradation of the mRNA, while a partial complementarity induces translational inhibition.
Small RNA-sequence analysis of plasma-derived extracellular vesicle miRNAs in smokers and patients with chronic obstructive pulmonary disease as circulating biomarkers
Published in Journal of Extracellular Vesicles, 2019
Isaac Kirubakaran Sundar, Dongmei Li, Irfan Rahman
Transfer RNAs (tRNAs) play an essential role in protein synthesis. There are two main types of tRNA-derived small RNAs (tsRNAs): tRNA-derived fragments (tRFs: 14–30 nucleotides long) and tRNA halves (31–40 nucleotides long). Recent studies have demonstrated that tsRNAs perform several biological functions such as acting as signalling molecules during stress responses, and serving as regulators of transcription, translation, DNA damage response, viral infections, cancer and neurodegeneration [15]. Furthermore, Piwi-interacting RNAs (piRNAs: 36–32 nucleotides long) have been shown to modulate gene expression pathways via interacting with Piwi proteins [16]. Prior studies on differentially expressed piRNAs were reported in several types of malignancies (lung, breast, gastric and colorectal cancers) [16]. However, to date, no study has been conducted to comprehensively analyze different types of small RNA species such as miRNAs, tRNAs and piRNAs in human plasma-derived EVs as circulating biomarkers in smokers and patients with COPD compared to non-smokers by small RNA-sequencing.
siRNA drug development against hepatitis B virus infection
Published in Expert Opinion on Biological Therapy, 2018
Robert Flisiak, Jerzy Jaroszewicz, Mariusz Łucejko
The posttranscriptional siRNA effector phases are carried out in the cytoplasm of the cell. As a result, the guide strand can be exposed to the target mRNA sequence, enabling connection to complementary base pairs. After careful siRNA pairing with the target mRNA, the Argonaut (Ago) function is activated by the Piwi domain of Ago protein. The Piwi domain induces degradation of mRNA [25]. Optimal length siRNAs consist of 21 nucleotides with two nucleotide 3′ overhangs [53]. The incision takes place between positions 10 and 11 with the nucleotide counting from the end of the 5′ end of the guide strand [54,55]. This leads to further degradation of the mRNA by exonucleases [56]. A single siRNA loaded in RNA-induced silencing complex (RISC) can degrade several mRNA molecules. Moreover, in addition to the canonical siRNAs, there are other dsRNA molecules that can effectively induce RNAi [57] (Figure 1).
The potential of circulating cell-free RNA as a cancer biomarker: challenges and opportunities
Published in Expert Review of Molecular Diagnostics, 2018
Ivan A. Zaporozhchenko, Anastasia A. Ponomaryova, Elena Yu Rykova, Pavel P. Laktionov
PIWI-interacting RNAs (piRNAs) are another class of short noncoding RNAs, associated with proteins from the distinct PIWI clade of the Argonaute family. These RNAs regulate gene expression at transcriptional and posttranscriptional levels, participate in transposon silencing, protect the integrity of the genomes of the germline cells, and regulate developmental timing [94]. However, more recently, they were also found to be expressed in somatic tissues, such as lung, liver, kidney, brain, and others, and aberrant piRNA expression has been linked to cancer progression and development [95,96]. Subsequently, significant amounts of piRNAs have been discovered in biological fluids, and some of them are reportedly associated with membrane vesicles [76]. Circulating piRNAs have only just came into focus as potential cancer biomarkers, but several candidates for further testing have already been identified, including piR-019825 for colorectal cancer, piR-001311 and piR-016658 in pancreatic cancer, and piR-016658 and piR-020496 in prostate cancer [76]. Further investigation of these RNAs may uncover more potential biomarkers.