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Rett Syndrome
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
They observed that these mice develop the same behavioral phenotype and neuropathology as mice with a global MECP2 deletion, indicating that postmitotic neurons have an ongoing requirement for MeCP2. Mutations in MECP2 thus are likely to lead to uncontrolled target gene expression in neurons while perhaps expression in other tissues remains repressed. An alternative hypothesis is that neurons are less tolerant of background transcriptional noise than other cell types.
Aging Epigenetics
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Vasily V. Ashapkin, Lyudmila I. Kutueva, Boris F. Vanyushin
One of the consequences of the age-associated DNA damage accumulation in somatic cells could be stochastic deregulation of gene expression manifested as increased cell-to-cell variations in gene expression. When the expression levels of seven housekeeping genes, three heart-specific genes, two protease-encoding genes, and three mitochondrial genes were measured in individual cardiomyocytes isolated from the ventricular heart tissue of young (6 months) and old (27 months) male mice, a highly significant increase in cell-to-cell variations of the expression levels of all nuclear genes was observed in old animals compared with young ones [7]. In contrast, no significant cell-to-cell variations were observed in the expression levels of mitochondrial genes. Noise is inherent in the basic process of transcription, especially in genes expressed at low levels. When cultured mouse embryonic fibroblasts were treated at early passages with 0.1 mM H2O2, a known generator of oxidative damage, cell-to-cell variations in gene expression were greatly increased. The effect was absent at 6 h after treatment, but was significant at 48 h, when the cell populations started to show an increased number of senescent cells. At nine days after treatment, almost all cells were senescent, and the increased cell-to-cell variations in gene expression were still highly significant. It is conceivable that a variety of persistent forms of damage to biological macromolecules, including random changes to DNA methylation and chromatin remodeling, could initiate a gradual increase in transcriptional noise introducing phenotypic variation among cells. Such variation may become detrimental to tissue functioning, which would explain many etiological characteristics of the aging process, most notably the highly variable progressive decline in organ functions.
Combining human platelet proteomes and transcriptomes: possibilities and challenges
Published in Platelets, 2023
Jingnan Huang, Johan W.M. Heemskerk, Frauke Swieringa
Interestingly, our analysis indicated that several proteins present in the combined platelet proteome are lacking the corresponding transcripts (Figure 2 and Table S1). These proteome-only proteins were mostly secretory (= plasma) proteins (C17) such as fibrinogen, likely present in the platelet open canicular system or endocytosed. And furthermore, a set of uncharacterized proteins (C22) and proteins of the intermediate cytoskeleton (C2). Of the latter, indeed keratins are common contaminants in a typical proteomic workflow. Distribution profiles of the relevant transcripts (level >0.20) in both platelets and megakaryocytes furthermore indicated high numbers of RNA genes and pseudogenes (Figure 2e–f). The majority of the RNA genes and pseudogenes were linked to protein encoding genes (i.e. same locations on the chromosome), thus suggesting a considerable amount of transcriptional “noise.”
CASC7: a LncRNA with potential clinical application
Published in International Journal of Radiation Biology, 2022
Non-coding RNAs (ncRNAs) refer to RNAs that often lack protein-coding capabilities. Emerging evidence shows that these non-coding transcripts are neither junk nor mere transcriptional noise, and have many essential biological functions (Marques and Ponting 2014; Jathar et al. 2017). The genome is heavily transcribed and produces thousands of long non-coding RNAs (lncRNAs), with more than 200 nucleotides and no translation into functional proteins (Statello et al. 2021). There are various ways to classify lncRNAs based on their locations, structures, functions, and transcriptional directions (Wang and Chang 2011). Compared with other non-coding RNAs (small nucleolar RNAs, small interfering RNAs and microRNAs), an lncRNA has not only a secondary structure, but also a possible three-dimensional structure. Researchers have described how lncRNA-Xist exploits and alters three-dimensional genome architecture to spread across the X chromosome (Engreitz et al. 2013). These characteristics give lncRNAs functions similar to those of RNAs and proteins (Chi et al. 2019). Furthermore, they have more spatial and temporal specificity and lower interspecific conservation compared with mRNAs (Gloss and Dinger 2018). Through these characteristics, lncRNAs can control an elevated number of cellular processes, including cell survival, senescence, division, differentiation and stress response, suggesting they are likely to be potential biomarkers.
Long non-coding RNA FENDRR reduces prostate cancer malignancy by competitively binding miR-18a-5p with RUNX1
Published in Biomarkers, 2018
Guanying Zhang, Guangye Han, Xinjun Zhang, Quanfeng Yu, Zeyu Li, Zhenhui Li, Jianchang Li
Using human transcriptome analysis, researchers have revealed that only a small part of genes are protein-coding and most of the transcribed RNAs are not translated (Kapranov et al.2007). The non-coding transcripts generally include ribosomal RNA (rRNA), transfer RNA (tRNA) and micro-RNAs (miRNA). Although these non-coding transcripts were once considered to be transcriptional “noise”, more and more evidence has shown they play important roles in various physiological and pathophysiological processes. Long non-coding RNAs (lncRNAs) with transcripts containing more than 200 nucleotides represents a less investigated class of non-coding RNAs (Chen et al.2013). The number of lncRNAs ranges from 10,000 to 20,0008 and only a small part of them has been identified. Emerging studies have shown that lncRNAs play crucial roles in the regulation of cell differentiation, proliferation and apoptosis (McHugh et al.2015). It should be highlighted that most identified lncRNAs are dysregulated in different types of cancer, playing an oncogenic or tumor suppressive role (Gibb et al.2011). Notably, lncRNAs are characterized by their tissue-specificity, which increase the possibility to use them as novel biomarkers and therapeutic targets (Crea et al.2014). It has been reported that lncRNAs have been implicated in PCa development and progression (Prensner et al.2011). FENDRR is an lncRNA with its gene 3099nts in length which located at chr3q13.31 and consists of four exons (Xu et al.2014). FENDRR is found to be specifically expressed in nascent lateral plate mesoderm and be essential for proper heart and body wall development in mouse (Grote et al.2013, Grote and Herrmann 2013). Through binding with both polycomb repressive complexe 2 (PRC2) and Trithorax group/MLL protein complexes (TrxG/MLL), FENDRR plays important roles in controlling chromatin structure and gene activity (Schuettengruber et al.2007, Khalil et al.2009). It is found that decreased expression of FENDRR is associated with poor prognosis in gastric cancer and FENDRR regulates gastric cancer cell metastasis by affecting fibronectin1 expression (Xu et al.2014). However, the biological role of FENDRR and its mechanism in PCa is not known.